Table of Contents
Conference Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
Conference Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3
Conference Co-Chairs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4
Conference Organizing Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4
Scientific Program Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5
NFID Staff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6
Invited Presenters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7
General Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
American with Disabilities Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
Conference Information Desk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
Conference Language . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
Conference Location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
General CME Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
Message Center . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
No Smoking Policy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
Poster Sessions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
Press Room . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
Program and Abstracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
Registration Fees and Hours . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
Speaker Ready Room and Audiovisual Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
Verification of Attendance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
Affiliated Events and Other Meetings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
Upcoming NFID and Collaborator Conferences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12
Hotel Floorplan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13
Program At-A-Glance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14
Final Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15
Abstracts of Invited Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36
Abstracts of Submitted Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45
Abstracts of Submitted Poster Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56
Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .67
Disclosure Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71
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Sixth Annual Conference
Conference Overview
The remarkable pace of biotechnology discovery is continuing unabated. New cytokines are identified, immune regulatory
pathways unraveled, promising adjuvants reported, and investigational products revealed to have high degrees of protection
for humans against viral diseases not yet vaccine preventable, such as human papilloma virus and herpes simplex. The
tools of vaccination are being applied therapeutically for various cancers and chronic conditions.
The Annual Conference on Vaccine Research provides high-quality, current reports of scientific progress featured in both
invited presentations and submitted abstracts. The disparate fields covered in both human and veterinary vaccinology
encourage valuable cross-fertilization of ideas and approaches among researchers otherwise focused on specific diseases or
methods.
The Conference has become the largest scientific meeting devoted exclusively to research on vaccines and associated
technologies for disease prevention and treatment through immunization. The Sixth Annual Conference on Vaccine
Research promises to maintain this tradition as the premier venue for cutting edge topics and issues. Leading international
experts will lead seminars and panel discussions on topical areas of basic immunology, product development, clinical
testing, regulation, and other aspects of vaccine research. Opportunities for networking and scientific collaboration critical
to advancing vaccine science and development will be available through audience discussions, poster presentations,
sponsored exhibits, and evening ceremonies and receptions.
Conference Objectives
At the conclusion of this conference, participants should be able to meet the following objectives:
Overall Conference Objectives
■
■
Discuss recent scientific advances that are contributing to progress in
the development of vaccines
Identify research opportunities and scientific challenges associated with
vaccine development, production, and distribution
Session Specific Objectives
Keynote Address
■ Characterize the attributes and functions of effector and memory T cells
Mary Lou Clements-Mann Memorial Lecture in Vaccine Sciences
Discuss the importance of overcoming financial obstacles and public
relations challenges to conduct high-visibility phase III trials of AIDS
vaccines in the absence of validated animal models or serologic
correlates of protection.
■
■
■
Vaccines for Zoonotic Diseases
Understand the role of vaccines in controlling leptospirosis in animals and
the impact of vaccines in reducing exposure and incidence of human
leptospirosis.
■ Discuss the current status of vaccines in clinical trials to prevent or control
Rift Valley Fever in humans and animals.
■ Describe the technology and use of live rabies vaccine in baits for wildlife
and how this strategy has eliminated or greatly reduced rabies in wildlife
populations.
■
Vaccine Supply: Global Crisis
Provide an overview of current trends in the worldwide supply and
distribution of vaccines.
■ Review factors that influenced shortfalls in vaccine supply in the U.S.
during 2002, and recommendations for reducing the likelihood of future
supply shortfalls.
■ Discuss the opportunities and challenges facing vaccine developers in
developing countries.
■
Long-term Impact of Vaccination Strategies on Disease
Epidemiology
■ Explain the predictions of mathematical models of the effect of
vaccination programs on the epidemiology of vaccine-preventable
diseases.
2
Discuss the possibility that vaccination programs result in the selection of
new or emerging serotypes of disease-causing organisms.
Discuss unexpected observations with respect to the epidemiology of polio
as they relate to the global effort to eradicate polio.
on Vaccine Research
Regulatory/Suppressor T Cells: Implications for Vaccinology
■ Explain the characteristics and functions of regulatory and
suppressor T cells.
■ Describe the roles of regulatory T cells in virus- and bacteriamediated diseases.
■ Discuss the roles that regulatory T cells play in response to
parasitic infections.
Acknowledgments
This conference is supported, in part, through unrestricted educational
grants from:
■
■
Vaccines Against Nosocomial Infections
■ Review scientific progress in the development of vaccines
against Staphylococcus.
■ Discuss approaches to developing a vaccine against
Pseudomonas.
■ Review the status of research on vaccines against respiratory
syncytial virus.
■ Describe the state of development of vaccines against
Clostridium difficile.
Vaccines and Biodefense
■ Describe approaches to managing the threat of bioterroristic
attacks on agriculture.
■ Identify new approaches to enhance the value and safety of
vaccines against anthrax.
■ Discuss new approaches to improving the safety profile of
vaccines against smallpox.
■ Evaluate evidence regarding the potential for weaponizing
arenaviruses.
(as of April, 2003)
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
Antigenics, Inc.
Aventis Pasteur
Baxter Healthcare
Becton Dickinson
Bioject, Inc.
Chiron Corporation
Coley Pharmaceutical Group
Dynport Vaccine Company
GlaxoSmithKline
Iomai Corporation
MedImmune
Merck Vaccine Division
PowderJect Vaccines, Inc.
U.S. Food and Drug Administration
VaxGen
Vical Incorporated
Wyeth Pharmaceuticals
Malaria Vaccines
Discuss new approaches and developments in the quest for
vaccines against malaria.
■ Review current understanding of the correlates of protection
against malaria.
■ Review how genomics may impact on malaria vaccine
development.
■ Describe progress in the development of vaccines to prevent
transmission of malaria.
■
Hot Topics in Immunology
Discuss factors influencing T and B cell immunodominance.
■ Describe the attributes of B cell epitopes.
■
3
Sixth Annual Conference
Conference Co-Chairs
William J. Martone, M.D.
National Foundation for Infectious Diseases
Bethesda, Maryland
N. Regina Rabinovich, M.D.
Bill and Melinda Gates Foundation
Seattle, Washington
Peter L. Nara, D.V.M., Ph.D.
Biological Mimetics, Inc.
Frederick, Maryland
Bruce G. Weniger, M.D.
Centers for Disease Control and Prevention
Atlanta, Georgia
Conference Organizing Committee
John D. Clemens, M.D.
International Vaccine Institute
Seoul, Korea
Betty Dodet
Foundation Merieux
Lyon Cedex, France
Cyril Gerard Gay, D.V.M., Ph.D.
U.S. Department of Agriculture
Beltsville, Maryland
Myron M. Levine, M.D., D.T.P.H.
Center for Vaccine Development
Baltimore, Maryland
William J. Martone, M.D.
Conference Co-Chair
Pamela M. McInnes, D.D.S.
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland
Karen Midthun, M.D.
Center for Biologics Evaluation and Resesarch
Bethesda, Maryland
4
Peter L. Nara, D.V.M., Ph.D.
Conference Co-Chair
David A. Neumann, Ph.D.
National Foundation for Infectious Diseases
Bethesda, Maryland
Gregory A. Poland, M.D.
International Society for Vaccines
Rochester, Minnesota
N. Regina Rabinovich, M.D.
Conference Co-Chair
Fran G. Sonkin
Albert B. Sabin Vaccine Institute
Washington, DC
Bernard A.M. Van der Zeijst, Ph.D.
Netherlands Vaccine Institute
Bilthoven, Netherlands
Bruce G. Weniger, M.D.
Conference Co-Chair
on Vaccine Research
Scientific Program Committee
Jacques Banchereau, Ph.D.
Baylor Institute for Immunology Research
Dallas, Texas
Stanley A. Plotkin, M.D.
Aventis Pasteur
Doylestown, Pennsylvania
Richard J. Duma, M.D., Ph.D.
Halifax Medical Center
Daytona Beach, Florida
N. Regina Rabinovich, M.D.
Conference Co-Chair
Diane E. Griffin, M.D., Ph.D.
Johns Hopkins University Bloomberg School of Public Health
Baltimore, Maryland
Paul-Henri Lambert, M.D.
Centre Medical Universitaire de Genéve
Geneva, Switzerland
Myron M. Levine, M.D., D.T.P.H.
Member, Conference Organizing Committee
William J. Martone, M.D.
Conference Co-Chair
Pamela M. McInnes, D.D.S.
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland
Gary J. Nabel, M.D., Ph.D.
National Institutes of Health
Bethesda, Maryland
Rino Rappaoli, Ph.D.
Chiron, SpA
Sienna, Italy
Harriet L. Robinson, Ph.D.
Emory University School of Medicine
Atlanta, Georgia
Connie Schmaljohn, Ph.D.
U.S. Army Medical Research Institute of Infectious Diseases
Ft. Detrick, Maryland
Ethan M. Shevach, M.D.
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland
George R. Siber, M.D.
Wyeth Vaccines
Pearl River, New York
Bruce G. Weniger, M.D.
Conference Co-Chair
Peter L. Nara, D.V.M., Ph.D.
Conference Co-Chair
David A. Neumann, Ph.D.
Chairperson, Conference Organizing and Scientific Program
Committees
Albert D. Osterhaus, D.V.M., Ph.D.
Erasmus University Rotterdam
Rotterdam, Netherlands
5
Sixth Annual Conference
NFID Staff
Executive Staff
Office Staff
Sharon Cooper-Kerr
Director, Events Planning
National Foundation for Infectious Diseases
Bethesda, MD
John Han
Charlotte Lazrus
Sheena L. Majette
Director, Continuing Medical Education
National Foundation for Infectious Diseases
Bethesda, MD
Len Novick
Executive Director
National Foundation for Infectious Diseases
Bethesda, Maryland
6
Volunteer Staff
Brenda Nara
on Vaccine Research
Invited Presenters*
Roy M. Anderson, FRS
Professor of Infectious Disease
Chair, Department of Infectious Disease
Imperial College of Medicine
London, United Kingdom
Yasmine Belkaid, M.D.
Assistant Professor
University of Cincinnati Children’s Hospital
Cincinnati, Ohio
Arthur M. Friedlander, M.D.
Senior Medical Scientist
U.S. Army Medical Research Institute of Infectious Diseases
Frederick, Maryland
Bruce Gellin, M.D., M.P.H.
Director, National Vaccine Program Office
Department of Health and Human Services
Washington, District of Columbia
Carole Bolin, D.V.M., Ph.D.
Michigan State University
East Lansing, Michigan
Barney S. Graham, M.D., Ph.D.
Chief, Viral Pathogenesis Laboratory and Clinical Trials Core
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland
Michael Brehm, Ph.D.
University of Massachusetts Medical School
Worcester, Massachusetts
Adrian V.S. Hill, F.R.C.P., D.Phil., D.M.
Wellcome Trust Centre for Human Genetics
Oxford, United Kingdom
Daniel J. Carucci, M.D.
Director, NMRC Malaria Program
United States Navy
Silver Spring, Maryland
Stephen L. Hoffman, M.D.
Sanaria, LLC
Gaithersburg, Maryland
Stephen C. Cochi, M.D., M.P.H.
Director, Global Immunization Division
Centers for Disease Control and Prevention
Atlanta, Georgia
Ron Dagan, M.D.
Director, Pediatric Infectious Disease Unit
Soroka Medical Center
Beer Sheva, Israel
Robert Daum, M.D.
Professor
The University of Chicago
Chicago, Illinois
Donald P. Francis, M.D., D.Sc.
President and Founder
VaxGen, Incorporated
Brisbane, California
Ruth A. Karron, M.D.
Associate Professor
Johns Hopkins University
Baltimore, Maryland
Karen L. Kotloff, M.D.
Professor of Pediatrics and Medicine
University of Maryland School of Medicine
Baltimore, Maryland
Samuel J. Landry, Ph.D.
Associate Professor
Tulane University Health Science Center
New Orleans, Louisana
*Speakers and presentations subject to change
(continued)
7
Sixth Annual Conference
Invited Presenters*
Antonio Lanzavecchia, M.D.
Director
Institute for Research in Biomedicine
Bellinzona, Switzerland
Charles E. Rupprecht, V.M.D., M.S., Ph.D.
Chief, Rabies Section
Centers for Disease Control and Prevention
Atlanta, Georgia
Kingston Mills, Ph.D.
Professor of Experimental Immunology
Trinity College
Dublin, Ireland
Allan Saul, Ph.D.
Associate Director, Malaria Vaccine Development Unit
National Institute of Allergy and Infectious Diseases
Rockville, Maryland
Julie B. Milstien, Ph.D.
Chief, International Regulatory Affairs Section
University of Maryland School of Medicine
Baltimore, Maryland
Ethan M. Shevach, M.D.
Chief, Cellular Immunology Section
National Institute of Allergy and Infectious Disesases
Bethesda, Maryland
John C. Morrill, D.V.M., Ph.D.
President
Orion Research and Management Services
Gatesville, Texas
Kenneth Tomer, Ph.D.
Leader, Mass Spectrometry Group
National Institute of Environmental Health Sciences
Research Triangle Park, North Carolina
Peter R. Paradiso, Ph.D.
Vice President, Scientific Affairs and Research Strategy
Wyeth Vaccines
West Henrietta, New York
Mark Wheelis, Ph.D.
University of California, Davis
Davis, California
Clarence J. Peters, M.D.
Director of Biodefense
University of Texas
Galveston, Texas
*Speakers and presentations subject to change
Gerald B. Pier, Ph.D.
Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Kanury V.S. Rao, Ph.D.
Head of Immunology
International Centre for Genetic Engineering and Biotechnology
New Delhi, India
8
on Vaccine Research
General Information
AMERICANS WITH DISABILITIES ACT
The Crystal Gateway Marriott Hotel is fully accessible to the public in accordance with the Americans with
Disabilities Act guidelines. If you have any special meeting needs or requirements, please contact either Sharon
Cooper-Kerr or a member of the hotel staff.
CONFERENCE INFORMATION DESK
The Conference Information Desk is located in the foyer area outside the Arlington Ballroom. Conference
staff will be available at the desk throughout the conference.
CONFERENCE LANGUAGE
The official language for the conference is English.
CONFERENCE LOCATION
All sessions of the conference will be held at:
Crystal Gateway Marriott
1700 Jefferson Davis Highway
Arlington, VA 22202
(703) 920-3230
GENERAL CME INFORMATION
The National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide Continuing Medical Education (CME) for physicians.
NFID takes responsibility for the content, quality, and scientific integrity of this CME activity.
The National Foundation for Infectious Diseases (NFID) designates this CME activity for a maximum of 20.6
credit hours in Category 1 of the Physician’s Recognition Award of the American Medical Association. Each
physician should claim only those hours of credit that he/she actually spent in the educational activity.
Designated CME Activities
Sessions designated with a CME
eligible for CME credit hours.
symbol have been approved for CME Credit. No other sessions are
CME Certificates
In order to ensure that you receive the CME credit hours to which you are entitled, please complete the
following:
1. Complete the CME application for credits enclosed in your conference packet.
2. Return your completed application and conference evaluation to conference staff at the Conference
Information Desk.
9
Sixth Annual Conference
CME Disclosures
In order for program sessions to be accredited, program presenters must disclose to the conference participants
any real or apparent conflict(s) of interest related to the content of their presentations. A summary of these
conflicts of interest is printed separately in this book under the heading Continuing Medical Education
Disclosures (see Table of Contents).
MESSAGES
All sleeping rooms in the Crystal Gateway Marriott Hotel are equipped with a voice mail system. This system is
accessible via the hotel operator using the house phone. In case of emergencies requiring immediate attention,
your party should call the general hotel number listed below and instruct the switchboard to deliver a message to
Sharon Cooper-Kerr or Sheena Majette at the Vaccine Research Conference Information Desk outside of the
Arlington Ballroom. The general hotel number is 1-703-920-3230.
NO SMOKING POLICY
The Crystal Gateway Marriott Hotel is a non-smoking facility except for specially designated guest rooms and
smoking areas of the hotel bars and restaurants. No smoking is allowed in any of the session rooms, coffee break
area or in the foyer adjoining the session rooms.
POSTER SESSIONS
Posters will be on display throughout the day on Tuesday, May 6 and Wednesday, May 7. Presenters will be at
their boards during scheduled breaks to answer questions and discuss their research. Posters will be located in
Arlington Ballroom Salon IV.
PRESS ROOM
NFID will have a Press Room located in the McClean room. Members of the press should sign in at the
Conference Information Desk during registration hours.
PROGRAM AND ABSTRACTS
Each registered participant will receive one complimentary copy of the Final Program and Abstract Book as part
of his/her registration fee. Additional copies, if available, can be purchased for $45. Orders for additional
copies can be taken at the Conference Information Desk starting Wednesday, May 7, and after the conference
by e-mail to vaccine@nfid.org, calling (301) 656-0003 x19, or by fax to (301) 907-0878.
REGISTRATION FEES AND HOURS
The onsite registration fee: US $400.00
Space is limited to the first 525 registrants. The registration fee includes a program/abstract book, continental
breakfast on each day of the conference, all scheduled coffee breaks, and the receptions on Monday and Tuesday.
Accommodations and additional meals are not included.
10
on Vaccine Research
Individuals interested in registering onsite may do so at the Conference Information Desk between the
following times:
Sunday, May 4 . . . . . . . . . . . . . . . . . . . . . . 7:00 p.m. – 9:00 p.m.
Monday, May 5 . . . . . . . . . . . . . . . . . . . . . 7:00 a.m. – 5:30 p.m.
Tuesday, May 6 . . . . . . . . . . . . . . . . . . . . . . 7:00 a.m. – 5:30 p.m.
Wednesday, May 7 . . . . . . . . . . . . . . . . . . . 8:00 a.m. – noon
Speaker Ready Room and Audiovisual Equipment
A room has been set aside for speakers to preview their slides. All speakers should check in at the Conference
Information Desk to be directed to the ready room. The room will be open during the registration hours (see
General Information – Registration Fees and Hours) and will be equipped with slide trays, slide previewers, a
laptop, and identification labels. Speakers are responsible for delivering and retrieving their properly labeled
slide trays to Sharon Cooper-Kerr or Sheena Majette at the Conference Information Desk.
Standard session room setup includes a PC, 250 zip drive, slide projector, laser pointer, podium microphone,
and aisle microphone.
Verification of Attendance
International attendees may obtain a letter of attendance verification from the staff at the Conference
Information Desk during registration hours.
Affiliated Events and Other Meetings
MONDAY, MAY 5, 2003
Conference on Vaccine Research Organizing Committee Meeting
(Closed meeting)
12:30 p.m. – 1:30 p.m., Tuscany’s Restaurant
Why Vaccine Advocacy Matters: An Action Agenda for the Research Community
(Luncheon)
12:30 p.m. – 1:30 p.m., Grand Ballroom, Salons F & G
Sponsored by the National Foundation for Infectious Diseases
This activity is supported by an unrestricted educational grant from Aventis Pasteur
Conference on Vaccine Research Scientific Program Committee Meeting
(Closed meeting)
7:00 – 9:30 p.m., Tuscany’s Restaurant
TUESDAY, MAY 6, 2003
Albert B. Sabin Vaccine Institute Award Ceremony and Reception
6:00 p.m. – 7:00 p.m., Arlington Foyer (Reception)
7:00 p.m. - 8:00 p.m., Arlington Ballroom (Ceremony)
11
Sixth Annual Conference
Upcoming NFID and Collaborator Conferences
JUNE 6–8, 2003
Infectious Diseases: A Course for Practicing Clinicians
Co-Sponsored by the National Foundation for Infectious Diseases and the Cleveland Clinic Foundation
The Renaissance Cleveland Hotel, Cleveland, Ohio
This course focuses on the epidemiology, recognition, therapy, and management of important infectious
diseases. Expert faculty will provide the latest information on both current and prospective therapeutic agents
through lectures, and interactive case presentations. For more information, visit the NFID website at
www.nfid.org or contact the NFID staff office at 301-656-0003 ext. 19
June 23-25, 2003
2003 Annual Conference on Antimicrobial Resistance
Sponsored by the National Foundation for Infectious Diseases
Hyatt Regency Bethesda, Bethesda, Maryland
This conference focuses on the science, prevention and control of antimicrobial resistance. For more
information, visit the NFID website at www.nfid.org or contact the NFID staff office at 301-656-0003 ext. 19.
May 10-21, 2004
Advanced Vaccinology Course
Organized by the Merieux Foundation
The Conference Center of the Merieux Foundation, Les Pensieres, France.
This two-week course is for scientists and decision-makers from the public and private sector involved in
vaccine development or in policy decisions related to the introduction of new vaccines in public health programs.
It provides a comprehensive overview of vaccinology. For more information: http://www.fondation-merieux.org
or contact Betty Dodet: betty.dodet@fondation-merieux.org; fax: (33) 4 72 40 79 50.
12
on Vaccine Research
Hotel Floor Plan
13
Sixth Annual Conference
PROGRAM-AT-A-GLANCE
SUNDAY, MAY 4
7:00
MONDAY, MAY 5
Registration
TUESDAY, MAY 6
WEDNESDAY, MAY 7
Registration
Registration
7:30
Continental Breakfast
Continental Breakfast
8:00
Symposium 3:
Vaccine Supply: Global Crisis
Symposium 6:
Vaccines for Zoonotic Diseases
Coffee Break/Posters/Exhbits
Coffee Break/Posters
Symposium 4:
Regulatory/Suppressor T Cells:
Implications for Vaccinology
Submitted Presentations 5
Submitted Presentations 6
8:30
Continental Breakfast
9:00
Welcome and Introductions
9:10
Keynote Address
9:45
9:50
Mary Lou Clements-Mann
Memorial Lecture
10:00
10:30
Coffee Break
11:00
Symposium 1:
Long-term Impact of
Vaccination Strategies on
Disease Epidemiology
Noon
Lunch
12:15
Lunch
12:30
Lunch
1:15
Symposium 5:
Symposium 7:
1:30
Vaccines Against Nosocomial
Infections
Malaria Vaccines
1:45
Submitted Presentations 1
Submitted Presentations 2
3:15
Coffee Break
Coffee Break/Posters/Exhbits
Coffee Break
3:45
Symposium 2:
Vaccines and Biodefense
Submitted Presentations 3
Submitted Presentations 4
Symposium 8:
Hot Topics in Immunology
Adjournment
Adjournment
5:30
5:45
Adjournment
6:00
Poster & Exhibit Reception
7:00
14
Registration
Albert B. Sabin Vaccine
Institute Reception
Presentation of the
Albert B. Sabin Gold Medal
on Vaccine Research
FINAL PROGRAM
SUNDAY, MAY 4, 2003
7:00 – 9:00 p.m.
Early Registration
Foyer-Arlington Ballroom
MONDAY, MAY 5, 2003
7:00 – 9:00 a.m.
Registration
Foyer-Arlington Ballroom
8:00 a.m.
Poster Set-Up
8:30 a.m.
Continental Breakfast
9:00 a.m.
Welcome and Introductions
Arlington Ballroom, Salon 4
Keynote Address CME
Moderator:
9:10 a.m.
1.
9:45 a.m.
Foyer-Arlington Ballroom
Arlington Ballroom, Salon 1/2/3
Arlington Ballroom, Salon 1/2/3
Ethan M. Shevach, M.D.
National Institute of Allergy and Infectious Diseases
Vaccination and Immunological Memory
Antonio Lanzavecchia, M.D.
Institute for Resesarch in Biomedicine
Questions and Answers
Mary Lou Clements-Mann Memorial Lecture in Vaccine Sciences
CME
Arlington Ballroom, Salon1/2/3
Moderator:
9:50 a.m.
2.
Bruce G. Weniger, M.D.
Centers for Disease Control and Prevention
Lessons from the World’s First Phase-III Field Efficacy Trials
of a Preventive AIDS Vaccine
Donald P. Francis, M.D., D.Sc.
VaxGen, Inc.
10:25 a.m.
Questions and Answers
10:30 a.m.
Coffee Break
15
Sixth Annual Conference
FINAL PROGRAM
MONDAY, MAY 5, 2003 (CONTINUED)
Symposium 1:
Long-Term Impact of Vaccination Strategies
on Disease Epidemiology CME
Moderators:
11:00 a.m.
3.
11:25 a.m.
11:30 a.m.
Paul-Henri Lambert, M.D.
Centre Medical Universitaire
Bruce G. Weniger, M.D.
Centers for Disease Control and Prevention
The Potential Public Health Impact of Imperfect HIV-1 Vaccines
To Be Announced
Questions and Answers
4.
11:55 a.m.
12:00 p.m.
Pneumococcal Conjugate Vaccines: What is the Risk of Post Vaccination
Emerging Serotypes and Replacement Disease?
Ron Dagan, M.D.
Ben-Gurion University
Questions and Answers
5.
Unexpected Challenges on the Road to Polio Eradication
Stephen C. Cochi, M.D., M.P.H.
Centers for Disease Control and Prevention
12:25 p.m.
Questions and Answers
12:30 p.m.
NFID Luncheon: Why Vaccine Advocacy Matters:
An Action Agenda for the Research Community
Submitted
Presentations 1:
Progress in Plant-made Vaccines
(Concurrent Sessions)
Moderator:
16
Arlington Ballroom, Salon 1/2/3
CME
Grand Ballroom, Salons F&G
Arlington Ballroom, Salon1/2/3
Rino Rappaoli, Ph.D.
Chiron, SpA
1:45 p.m.
S1
Vaccine Production Using Plant Virus Vectors
A. V. Karasev, H. Koprowski
Department of Microbiology and Immunology, Thomas Jefferson University, Doylestown, PA.
2:00 p.m.
S2
Expression of Foot and Mouth Disease Viral Antigens in Transgenic Alfafa Plants
A. Wigdorovitz
Virology Department, National Institute of Agriculture, Buenos Aires, ARGENTINA.
on Vaccine Research
FINAL PROGRAM
2:15 p.m.
S3
Plant Virus Particle-Based Candidate Vaccine Against Respiratory Syncytial Virus
V. M. Yusibov1, C. Davidson1, V. Mett1, S. Gilliam2, T. McVetty2, D. Mann2
1Center for Molecular Biotechnology, Fraunhofer USA, Newark, DE,
2University of Maryland, Baltimore, MD.
2:30 p.m.
S4
Immunogenicity of a Recombinant Bacterial Antigen Delivered in Transgenic Corn
C.O. Tacket1, J.D. Clements2, S.S. Wasserman1, S.J. Streatfield2
1Center for Vaccine Development, University of Maryland School of Medicine,
Baltimore, MD, 2Microbiology & Immunology, Tulane University School of Medicine,
New Orleans, LA, 3Molecular Biology, Prodigene, College Station, TX.
2:45 p.m.
S5
Clinical Response in Chickens Following the Administration of Plant-Made Vaccine Against
Newcastle Disease Virus
T. J. Miller1, M. Fanton1, M. Fanton1, G. Cardineau2, H. S. Mason3, C. Artzen3
1Benchmark Biolabs Inc, Lincoln, NE, 2Dow AgroSciences LLC, Indianapolis, IN,
3Arizona State University, Tempe, AZ.
3:00 p.m.
S6
Model Production of a Potent Plant-Made Vaccine
D. D. Kirk, W. Vonhof, J. Eibner, H. Mason, X. Zhang
Boyce Thompson Institute for Plant Research, Ithaca, NY.
3:15 p.m.
Coffee Break
Submitted
Presentations 2:
Vaccines Against Potential Bioweapons CME
(Concurrent Session)
Moderator:
Arlington Ballroom, Salon 5/6
Richard J. Duma, M.D., Ph.D.
Halifax Medical Center
1:45 p.m.
S7
Comparison of Three Assays Used for T Cell Epitope Mapping in Ebola Virus:
IFN-γγ Enzyme-Linked Immunospot (ELISpot), IFN-γγ Intracellular Cytokine Staining,
and 51Cr-Release
M. A. Bailey
Department of Virology, USAMRIID, Fort Detrick, MD.
2:00 p.m.
S8
Intranasal Proteosome™ Based F1V Vaccine Elicits Respiratory and Serum
Antibody Responses and Protects Mice Against Lethal Aerosolized Plague Infection
T. Jones1, J. Adamovicz 2, J. Anderson2, C. Bolt2, D. Burt1, M. Pitt2, G. Lowell1
1ID
Biomedical Corp of Quebec, Montreal, PQ, CANADA, 2US Army Medical Research
Institute of Infectious Disease, Ft Detrick, MD.
17
Sixth Annual Conference
FINAL PROGRAM
MONDAY, MAY 5, 2003 (CONTINUED)
2:15 p.m.
S9
Evaluation of a Genetically Modified Live Attenuated Vaccine for Venezuelan Equine
Encephalitis
D. S. Reed1, M. Hart2, W. Pratt2, C. Lind2, P. Gallagher1, M. Lackemeyer1,
M. Parker2
1Department of Aerobiology, United States Army Medical Research Institute of Infectious
Diseases (USAMRIID), Frederick, MD, 2Department of Virology, USAMRIID,
Frederick, MD.
2:30 p.m.
S10 Decreased Immunogenicity of Botulinum Pentavalent Toxoid to Toxins B and E
J. M. Rusnak1, L. Smith2, E. Boudreau1, S. Norris3, T. Cannon4, D. Clizbe1,
M. Kortepeter1
1Special Immunizations Clinic, USAMRIID, Fort Detrick, MD, 2Department of
Toxinology, USAMRIID, Fort Detrick, MD, 3USAMRIID, Fort Detrick, MD,
4USAMISSA, Fort Detrick, MD.
2:45 p.m.
S11 Efficacy of an Oral, Inactivated Whole-Cell Enterotoxigenic E. coli/Cholera Toxin B Subunit
Vaccine in Egyptian Infants
S. Savarino1, R. Abu-Elyazeed2, M. Rao3, R. Frenck2, I. Abdel-Messih2, E. Hall1,
S. Putnam2, H. El-Mohamady2, T. Wierzba2, B. Pittner2, K. Kamal2, P. Moyer3,
B. Morsy4, A. Svennerholm4, Y. Lee3, J. Clemens6
1Naval Medical Research Center, Silver Spring, MD, 2Naval Medical Research–Unit 3,
Cairo, EGYPT, 3National Institute of Child Health and Human Development,
Bethesda, MD, 4Ministry of Health, Cairo, EGYPT, 5University Goteborg, Goteborg,
SWEDEN, 6IVI, Seoul, REPUBLIC OF KOREA.
3:00 p.m.
S12 Expected but Unusual Rashes in Adults after First Vaccinia Vaccination
R. N. Greenberg1, B. A. Plummer1, S. A. Roberts1, M. A. Caldwell1, D. L. Hargis1,
R. J. Hopkins2
1Department of Medicine, University of Kentucky, Lexington, KY, 2Dynport Vaccine
Company, LLC, Frederick, MD.
3:15 p.m.
Symposium 2:
Coffee Break
Vaccines and Biodefense
Moderators:
18
CME
Arlington Ballroom, Salon 1/2/3
Connie Schmaljohn, Ph.D.
U.S. Army Medical Research Institute of Infectious Diseases
Gary J. Nabel, M.D., Ph.D.
National Institutes of Health
on Vaccine Research
FINAL PROGRAM
3:45 p.m.
6.
4:10 p.m.
4:15 p.m.
Questions and Answers
7.
4:40 p.m.
4:45 p.m.
Anthrax: Issues and Answers
Arthur M. Friedlander, M.D.
U.S. Army Medical Research Institute of Infectious Diseases
Questions and Answers
8.
5:10 p.m.
5:15 p.m.
Agricultural Bioterrorism: Managing the Threat
Mark Wheelis, Ph.D.
University of California, Davis
New Strategies for Safer Smallpox Vaccines
Barney S. Graham, M.D., Ph.D.
National Institutes of Health
Questions and Answers
9.
South American Arenaviruses: Will They Emerge as Threats?
Clarence J. Peters, M.D.
University of Texas Medical Branch
5:40 p.m.
Questions and Answers
5:45 p.m.
Adjournment
6:00 p.m.
Poster and Exhibit Reception
Arlington Ballroom, Salon 4
TUESDAY, MAY 6, 2003
7:00-8:00 a.m.
Registration
Foyer-Arlington Ballroom
7:30 a.m.
Continental Breakfast
Foyer-Arlington Ballroom
Symposium 3:
Vaccine Supply: Global Crisis
Moderators:
CME
Arlington Ballroom, Salon 1/2/3
Myron M. Levine, M.D., D.T.P.H.
University of Maryland School of Medicine
Bruce G. Weniger, M.D.
Centers for Disease Control and Prevention
19
Sixth Annual Conference
FINAL PROGRAM
TUESDAY, MAY 6, 2003 (CONTINUED)
8:00 a.m.
8:25 a.m.
8:30 a.m.
8:55 a.m.
9:00 a.m.
9:25 a.m.
9:30 a.m.
10. Global Trends and Issues in Vaccine Supply
Julie B. Milstien, Ph.D.
University of Maryland School of Medicine
Questions and Answers
11. Vaccination Supply Crises in USA 2002: A Government Perspective
Bruce Gellin, M.D., M.P.H.
Department of Health and Human Services
Questions and Answers
12. Vaccine Supply Crises in the USA 2002: An Industry Perspective
Peter R. Paradiso, Ph.D.
Wyeth Vaccines and Nutrition
Questions and Answers
13. Supplying New Developing Market Vaccines: Role of the Vaccine Industry in
Developing Countries
To Be Announced
9:55 a.m.
Questions and Answers
10:00 a.m.
Coffee Break/Posters
Symposium 4:
Regulatory/Suppressor T Cells:
Implications for Vaccinology CME
Moderator:
10:30 a.m.
10:55 a.m.
11:00 a.m.
20
David A. Neumann, Ph.D.
National Foundation for Infectious Diseases
14. Regulatory/Suppressor T Cells: An Overview
Ethan M. Shevach, M.D.
National Institutes of Health
Questions and Answers
15. Regulatory T Cells in Viral and Bacterial Diseases
Kingston Mills, Ph.D.
Trinity College, Dublin
Arlington Ballroom, Salon 4
Arlington Ballroom, Salon 1/2/3
on Vaccine Research
FINAL PROGRAM
11:25 a.m.
11:30 a.m.
Questions and Answers
16. Role of CD4+ CD25+ Regulatory T Cells in Leishmania Infection
Yasmine Belkaid, M.D.
University of Cincinnati
11:55 a.m.
Questions and Answers
12:00 p.m.
Lunch
Symposium 5:
Vaccines Against Nosocomial Infections CME
Moderator:
1.15 p.m.
Questions and Answers
18. Towards the Development of a Pseudomonas Vaccine
Gerald B. Pier, Ph.D.
Harvard Medical School
2:10 p.m.
2:15 p.m.
Questions and Answers
19. Update on a Vaccine for Respiratory Syncytial Virus
Ruth A. Karron, M.D.
Johns Hopkins University
2:40 p.m.
2:45 p.m.
Salon 1/2/3
William J. Martone, M.D.
National Foundation for Infectious Diseases
17. A Vaccine Against Staphylococcus aureus
Robert Daum, M.D.
The University of Chicago
1:40 p.m.
1:45 p.m.
`
Arlington Ballroom,
Questions and Answers
20. Development of a Vaccine Against Clostridium difficile
Karen L. Kotloff, M.D.
University of Maryland
3:10 p.m.
Questions and Answers
3:15 p.m.
Coffee Break/ Posters
Arlington Ballroom, Salon 4
Submitted
Presentations 3
Vaccines for HIV and Other Sexually Transmitted Diseases
(Concurrent Session)
Moderator:
William J. Martone, M.D.
National Foundation for Infectious Diseases
CME
Arlington Ballroom, Salon 1/2/3
21
Sixth Annual Conference
FINAL PROGRAM
TUESDAY, MAY 6, 2003 (CONTINUED)
22
3:45 p.m.
α, MIP-3α
α and MIP-3β
β on the Induction of Gag-Specific
S13 The Adjuvant Effects of MIP-1α
Immunity with HIV-1 DNA Vaccine
R. Song1, S. Liu2, J. Wen2, K. W. Leong2
1Department of Pharmacology, Johns Hopkins University, Baltimore, MD,
2Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD.
4:00 p.m.
S14 Differences in Conformation and Epitope Exposure Between Neutralization Resistant Primary
and Neutralization Sensitive T-Cell Line Adapted HIV-1
M. Leavitt1, P. Bouma1, C. Broder1, D. Dimitrov2, J. Robinson3, S. Zolla-Pazner4,
G. Quinnan1
1Uniformed Services of the Health Sciences, Bethesda, MD, 2National Cancer Institute,
Frederick, MD, 3Tulane University Medical Center, New Orleans, LA, 4Veterans Affairs
Medical Center, New York, NY.
4:15 p.m.
S15 DNA Encoding a HIV-1 Gag/lysosome-Associated Membrane Protein (LAMP) Chimera Elicits
Strong B- and T-Cell Gag-Specific Immune Responses in Rhesus Monkeys
P. R. Chikhlikar1, L. Barros de Arruda1, M. Maciel Jr1, B. Byrne2, P. Silvera3,
M. Lewis3, E. T.A. Marques1, J. Thomas August1
1Department of Pharmacology and Molecular Sciences, The Johns Hopkins
University-School of Medicine, Baltimore, MD, 2University of Florida, Gaineszille, FL,
3Infectious Disease Research, Southern Research Institute, Frederick, MD.
4:30 p.m.
S16 Evaluation of a Subunit Vaccine Formulation Containing HSV-2 gD and IL-12 or MPL in
Prophylactic and Therapeutic Guinea Pig Models of Genital Herpes
J. Strasser1, S. Gangolli2, J. Kowalski2, C. Chaulk1, S. Bhargava2, A. Abramovitz2,
D. Bernstein1, T. Zamb2, D. Long2
1Department of Infectious Diseases, Children’s Hospital Medical Center, Cincinnati, OH,
2Viral Vaccine Research, Wyeth Research, Pearl River, NY.
4:45 p.m.
S17 Mucosal Immunization with a Recombinant Chlamydia Trachomatis High Molecular Weight
Protein Protects Mice Against Heterotypic Genital Infection
H. Lu, A. M. Harris, G. S. Nabors, W. J. Jackson
Antex Biologics, Gaithersburg, MD.
5:00 p.m.
S18 An Hsp65-HBV Core Antigen Fusion Protein Primes HbcAg-Specific CTL Responses in
Immunologically Tolerant HBV Transgenic Mice
L. S. D. Anthony1, S. G. Winslow2, H. Liu1, G. Rowse1, B. Wu1, A. Recktenwald1,
J. G. Julander2, L. A. Mizzen1, J. D. Morrey2, M. I. Siegel3
1Stressgen Biotechnologies Corporation, Victoria, BC, CANADA, 2Utah State University,
Logan, UT, 3Stressgen Biotechnologies Inc., Collegeville, PA.
on Vaccine Research
FINAL PROGRAM
5:15 p.m.
S19 SIV env gp140 “Domain-Specific” Antibody Responses in Rhesus Macaques
Inoculated with Attenuated SIV/17E: A Novel Strategy to Understanding
Delayed Humoral Immunity
J. L. Rowles, K. S. Cole, M. Murphey-Corb, R. C. Montelaro;
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of
Medicine, Pittsburgh, PA.
Submitted
Presentations 4
Vaccines Against Familiar Bacterial Diseases
(Concurrent Session)
Moderator:
CME
Arlington Ballroom, Salon 5/6
N. Regina Rabinovich, M.D.
Bill and Melinda Gates Foundation
3:45 p.m.
S20 Benefits of NonTypeable Haemophilius influenzae Vaccines That Prevent Transmission
Compared to Those That Prevent Disease Given Transmission
J. S. Koopman, X. Lin
Department of Epidemiology, University of Michigan, Ann Arbor, MI.
4:00 p.m.
S21 Safety and Immunogenicity of Two Formulations of a Hexavalent Diphtheria-Tetanus-Acellular
Pertussis-Inactivated Poliovirus-Haemophilus influenzae B Conjugate-Hepatitis B Vaccine in
15-18 Month Old Children
S. A. Halperin1, J. M. Langley1, T. M. Hesley2, P. S. Zappacosta2, D. Radley2,
A. Hoffenbach3, J. L. Silber4
1Department of Pediatrics, Dalhousie University, Halifax, NS, CANADA,
2Merck & Co., Inc., West Point, PA, 3Aventis Pasteur, Swiftwater, PA, 4Merck & Co., Inc,
West Point, PA.
4:15 p.m.
S22 Development of Live Attenuated Shigella Vaccines that Express Both (ETEC) CFA/I Fimbrial
Protein and the B Subunit of Heat-labile Toxin (LT-B).
R. T. Ranallo, F. Cassels, A. Hartman, M. Venkatesan;
Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, MD.
4:30 p.m.
S23 Lipopolysaccharide Shigella sonnei Vaccine: From Development to Clinical Application
P. G. Aparin1, L. I. Pavlova2, R. P. Chuprinina2, M. E. Golovina1, S. I. Elkina3,
V. I. Shmigol1, T. V. Gantcho3, V. L. L’vov1
1NRC-Institute of Immunology, Moscow, RUSSIAN FEDERATION, 2Natl Institute
Biological Standartization MOH, Moscow, RUSSIAN FEDERATION, 3ATV D-TEAM
Co., Ltd, Moscow, RUSSIAN FEDERATION
4:45 p.m.
S24 Mass Vaccination Campaign Against Meningococcal C Disease in the Netherlands
G. P. J. van den Dobbelsteen1, L. van Alphen2, T. F. A. Veerman1,
B. A. M. van der Zeijst1
1Netherlands Vaccine Institute, Bilthoven, NETHERLANDS, 2Laboratory for
Vaccine Research, Netherlands Vaccine Institute, Bilthoven, NETHERLANDS
23
Sixth Annual Conference
FINAL PROGRAM
TUESDAY, MAY 6, 2003 (CONTINUED)
5:00 p.m.
5:15 p.m.
S25 Human Bactericidal Antibodies Against Group A Streptococci (GrAS)
Induced by StreptAvax™, a 26-Valent M Protein-Based Vaccine
P. Vink1, J. Dale2, M. Chao-Hong Hu3, M. Reddish3, S. Stroop3, S. McNeil4,
J. Langley4, S. Halperin4, B. Smith4
1ID Biomedical of Maryland, Baltimore, MD, 2VA Medical Center and University
of Tennessee, Memphis, TN, 3ID Biomedical of Washington, Bothell, WA,
4Dalhousie University, Halifax, NS, CANADA.
S26 Safety and Immunogenicity of a Booster Dose of StaphVAX®, a
Staphylococcus aureus Conjugate Vaccine in Previously Immunized
Hemodialysis Patients
A. I. Fattom, S. Fuller, S. Winston, R. Naso, G. Horwith
Research&Development, Nabi Biopharmaceuticals, Rockville, MD.
5:30 p.m.
Adjournment
6:00 p.m.
Albert B. Sabin Vaccine Institute Reception
7:00 p.m.
Presentation of the Albert B. Sabin Gold Medal
Foyer-Arlington Ballroom
Arlington Ballroom
WEDNESDAY, MAY 7, 2003
7:00-8:00 a.m.
Registration
Foyer-Arlington Ballroom
7:30 a.m.
Continental Breakfast
Foyer-Arlington Ballroom
Symposium 6:
Vaccines for Zoonotic Diseases
Moderators:
8:00 a.m.
8:30 a.m.
24
CME
Arlington Ballroom, Salon 1/2/3
David E. Swayne, D.V.M., Ph.D.
U.S. Department of Agriculture
Richard J. Duma, M.D., Ph.D.
Halifax Medical Center
21. New Paradigms of Leptospiral Immunity and Impact on Vaccine Design
Carole Bolin, D.V.M., Ph.D.
Michigan State University
Questions and Answers
on Vaccine Research
FINAL PROGRAM
8:40 a.m.
22. Current Status of Rift Valley Fever Virus Vaccines
John C. Morrill, D.V.M., Ph.D.
Orion Research and Management Services
9:10 a.m.
9:20 a.m.
Questions and Answers
23. Rabies Vaccines: Past, Present and Future
Charles E. Rupprecht, V.M.D., M.S., Ph.D.
Centers for Disease Control
9:50 a.m.
Questions and Answers
10:00 a.m.
Coffee Break/Posters
Submitted
Presentations 5
Antiviral Vaccines
(Concurrent Session)
Moderator:
Arlington Ballroom, Salon 4
CME
Arlington Ballroom, Salon 1/2/3
Stanley A. Plotkin, M.D.
Aventis Pasteur
10:30 a.m.
S27 Induction of T-Cell Mediated Immune Responses by HLA Class II-Restricted Naturally
Processed Measles Virus Peptides
I.G. Ovsyannikova, K. L. Johnson, J. E. Ryan, R. C. Howe, D. C. Muddiman,
G. A. Poland
Vaccine Research Group and the W. M. Keck FT-ICR Mass Spectrometry Laboratory,
Mayo Clinic and Foundation, Rochester, MN.
10:45 a.m.
S28 A Measles DNA Vaccine Augmented with IL-2 Protects Infant Monkeys in the Presence of
Neutralizing Antibody
M.F. Premenko-Lanier1, P.Rota2, G. Rhodes1, D. Barouch3, N. Letvin3, W. Bellini2,
M. McChesney1
1University of California at Davis, Davis, CA, 2Centers for Disease Control and
Prevention, Atlanta, GA, 3Harvard Medical School, Boston, MA.
11:00 a.m.
S29 Mumps virus: Changes in virus gene sequence associated with variability in
neurovirulence phenotype
S. A. Rubin1, G. Amexis1, M. Pletnikov2, K. Chumakov1, K. Carbone1
1Food and Drug Administration/Center for Biologics Evaluation and Research,
Bethesda, MD, 2Johns Hopkins University, Baltimore, MD.
11:15 a.m.
S30 Rotavirus VP6 Protein Formulated with Polyphosphazene Adjuvants Induce Protection in a
Mouse Challenge Model
A.H. Choi1, J. Chen2, A. K. Andrianov2, M. M. McNeal1, M. Basu1, R. L. Ward1
1Division of Infectious Diseases, Cincinnati Children’s Hospital Research Foundation,
Cincinnati, OH, 2Parallel Solutions, Inc., Cambridge, MA.
25
Sixth Annual Conference
FINAL PROGRAM
WEDNESDAY, MAY 7, 2003 (CONTINUED)
11:30 a.m.
S31 Intranasal or Oral Immunization of Mice with VP6, a New Rotavirus Vaccine Candidate,
Consistently Protects Mice Against Viral Shedding After Rotavirus Challenge
R. L. Ward, M. M. McNeal, M. Basu, A. H. C. Choi
Division of Infectious Diseases, Children’s Hospital Medical Center, Cincinnati, OH.
11:45 a.m.
S32 Aggregate Content Influences the Type 1:Type 2 Immune Response to Influenza Vaccine:
Evidence from a Mouse Model
D. M. Skowronski1, S. Babiuk2, G. De Serres3, K. Hayglass4, R. C. Brunham1,
L. Babiuk2
1Epidemiology Services, UBC Centre for Disease Control, Vancouver, BC, CANADA,
2Veterinary Infectious Disease Organization, Saskatoon, SK, CANADA, 3Institut National
de Sante Publique de Quebec, Quebec City, PQ, CANADA, 4Department of Immunology,
University of Manitoba, Winnipeg, MB, CANADA.
12:00 p.m.
S33 Risk of Recurrence of Oculo-Respiratory Syndrome (ORS) Associated with Two Different
Influenza Vaccines for 2002-2003
G. De Serres1, D. M. Skowronski2, M. Guay3, L. Rochette1, K. Jacobsen4, T. Fuller4,
M. Dionne1, B. Duval1
1Institut National de Santé Publique du Québec, Beauport, Québec, PQ, CANADA,
2BC Centre for Disease Control, Vancouver, BC, CANADA, 3Institut national de santé
publique du Québec, Longueil,, PQ, CANADA, 4Westcoast Clinical Research, Coquitlam,
BC, CANADA.
Submitted
Presentations 6
Progress in New Vaccine Development
(Concurrent Session)
Moderators:
10:30 a.m.
26
CME
Arlington Ballroom, Salon 5/6
David A. Neumann, Ph.D.
National Foundation for Infectious Diseases
Peter L. Nara, D.V.M., Ph.D.
Biological Mimetics, Inc.
S34 Original Antigenic Sin and Malaria Subunit Vaccines: The Effect of Plasmodium Yoelii
Exposure on Vaccination with 19 kDa Carboxylterminus of the Merozoite Surface Antigen 1
(MSP119) and Vice Versa
J. Wipasa1, C. Hirunpetcharat2, A. Stowers3, M. F. Good1, H. Xu1
1Queensland Institute of Medical Research, Brisbane, AUSTRALIA, 2Mahidol
University, Bangkok, THAILAND, 3National Institutes of Health, Bethesda, MD.
on Vaccine Research
FINAL PROGRAM
10:45 a.m.
S35 Cell Mediated Immune (CMI) Responses to Oral BCG Moreau RdJ in Health Human Volunteers
C. Cosgrove1, L.L.R. Castello-Branco2, R. Giemza1, A. Sexton1, G.E. Griffin1,
D.J.M. Lewis1
1Department of Infectious Disease, St George’s Hospital Medical School, London,
UNITED KINGDOM, 2Fundacao Ataulpho de Paiva/Dept Clinical Immunology,
Fundacao Oswaldo Cruz, Rio de Janeiro, Brasil
11:00 a.m.
S36 Identification of a Protective 30KDa Antigen of Helicobacter Pylori
R. G. Keefe, G. S. Nabors, J. Tain, R. I. Walker, Y. Feng, R. Harris, W. J. Jackson
Antex Biologics, Gaithersburg, MD.
11:15 a.m.
S37 Vaccine Immunity to Pathogenic Fungi Overcomes the Requirement for CD4 Help in
Exogenous Antigen Presentation to CD8+ T-Cells: Implications for Vaccine Development
in Immunedeficient Hosts
M. Wuethrich1, H. I. Filutowicz1, T. Warner2, G. S. Deepe, Jr.3, B. S. Klein1
1Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, 2Department
of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI,
3Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH.
11:30 a.m.
S38 Peptide Mimotope of the Polysaccharide Capsule of Cryptococcus Neoformans Identified
from an Evolutionary Phage Display Library
R. J. May, Beenhouwer, Scharff
Cell Biology, Albert Einstein College of Medicine, Bronx, NY.
11:45 a.m.
S39 Induction of Multispecific Th-1 Type Immunity in Mice Against HCV by
Protein Immunization Using CpG and Montanide ISA 720
R. Wang, Q. Qiu, T. Grandinetti, L. Taylor, H. Alter, J. Shih
Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD.
12:00 p.m.
S40 HCV E2 DNA Vaccine with Improved Expression and Immunogenicity
S. Biswas, S. Lu
University of Massachusetts Medical School, Worcester, MA.
12:15 p.m.
Symposium 7:
Lunch
Malaria Vaccines
Moderator:
1:15 p.m.
CME
Arlington Ballroom, Salon 1/2/3
N. Regina Rabinovich, M.D.
Bill and Melinda Gates Foundation
24. Progress Report on Malaria Vaccines
Stephen L. Hoffman, M.D.
Sanaria, LLC
27
Sixth Annual Conference
FINAL PROGRAM
WEDNESDAY, MAY 7, 2003 (CONTINUED)
1:30 p.m.
1:35 p.m.
1:50 p.m.
1:55 p.m.
2:10 p.m.
2:15 p.m.
Questions and Answers
25. Immune Correlates of Protection
Adrian V.S. Hill, M.R.C.P., D.M., D.Phil.
Wellcome Trust Centre for Human Genetics
Questions and Answers
26. Translating the Malaria Genome
Daniel J. Carucci, M.D.
United States Navy
Questions and Answers
27. Transmission Blocking Vaccines
Allan Saul, Ph.D.
National Institutes of Health
2:30 p.m.
Questions and Answers
2:35 p.m.
Panel Discussion: Issues in the Design of Malaria Vaccine Field Trials
3:15 p.m.
Coffee Break
Symposium 8:
Hot Topics in Immunology
Moderators:
3:45 p.m.
4:05 p.m.
4:10 p.m.
28
CME
Arlington Ballroom, Salon 1/2/3
Peter L. Nara, D.V.M., Ph.D.
Biological Mimetics, Inc.
28. Antigen-Specific Early Primary Humoral Responses Modulate
Immunodominance of B Cell Epitopes
Kanury V.S. Rao, Ph.D.
International Centre for Genetic Engineering and Biotechnology
Questions and Answers
29. Structural Basis for T and B Cell Immunodominance
Samuel J. Landry, Ph.D.
Tulane University Health Science Center
on Vaccine Research
FINAL PROGRAM
4:30 p.m.
4:35 p.m.
Questions and Answers
30. T Cell Immunodominance and Memory Relative to Crossreactive Pathogens
Michael Brehm, M.D.
University of Massachusetts Medical Center
4:55 p.m.
5:00 p.m.
Questions and Answers
31. Mass Spectrometric Fine Determination of B Cell Epitopes
Kenneth Tomer, Ph.D.
National Institute of Environmental Health Science
5:20 p.m.
Questions and Answers
5:25 p.m.
Participant Evaluation
5:30 p.m.
Adjournment
Poster Group 1:
Scientific Advances in Vaccinology
P1
Immunological Bioinformatics
O. Lund, C. Lundegaard, P. Worning, M. Nielsen, S. Brunak
Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby,
DENMARK
P2
An In-situ Gelling Nasal Vaccine Delivery Platform
Y. Ni1, L. Tian2, K. M. Yates1, I. Tizard2
1DelSite
Biotechnologies Inc, Irving, TX, 2Department of Veterinary Pathobiology,
Texas A&M University, College Station, TX
P3
The synthetic triacyl pseudodipeptide OM-197-MP-AC induces the maturation of functional
monocyte-derived human dendritic cells able to induce primary T cell responses.
B. Byl1, M. Libin1, J. Bauer2, C. Chiavaroli2, O. Martin3, D. De Wit1, G. Davies2,
M. Goldman1, F. Willems1
1Laboratoire d’Immunologie Expérimentale, Université Libre de Bruxelles, Bruxelles,
BELGIUM, 2R&d, OM PHARMA, Meyrin, SWITZERLAND, 3Institut de Chimie
Organique et Analytique, Université d’Orleans, Orléans, FRANCE
P4
Efficacy of Adjuvants in developing vaccines: Calcium Phosphate nanoparticle Vs. Alum –
A Comparison
P. R. Nagappan, T. Morcol, A. R. Mitchell, L. Nerenbaum, Q. He, S. J. D. Bell
BioSante Pharmaceuticals, Inc., Smyrna, GA
29
Sixth Annual Conference
FINAL PROGRAM
P5
Adjuvanticity and Other Immunomodulatory Effects Associated with Lactobacillus reuteri
Colonization of the Gastrointestinal Tract.
W. J. Dobrogosz1, E. Connolly2
1Department of Microbiology, North Carolina State University, Raleigh, NC,
2BioGaia AB, Stockholm, SWEDEN
Poster Group 2:
P6
A novel group of very potent non-CpG Immunostimulatory Oligonucleotides
A. D. Montaner
Instituto de Investigaciones Biomédicas, Fundación Pablo Cassará., Buenos Aires,
ARGENTINA
P7
Strong CpG Independent Immunostimulation in Humans and other Primates by Synthetic
Oligodeoxynucleotides with PyNTTTTGT Motifs
A. D. Montaner, Sr.
Instituto de Investigaciones Biomédicas, Fundación Pablo Cassará., Buenods Aires,
ARGENTINA
P8
In Vitro CMI: A Rapid Assay to Determine Antigen-specific T-cell Function in Response to
Vaccination
J. B. Woodcock, R. J. Kowalski, J. A. Britz
Cylex Incorporated, Columbia, MD.
P9
Immunological Assays to Monitor Immune Responses to the Tumor Antigen CYP1B1.
M. I. Matijevic, J. Sathiyaseelan, R. G. Urban
Clinical Assays, ZYCOS Inc., Lexington, MA
Vaccines Against Bacterial Pathogens
P10 Phase I Study of Meningococcal Outer Membrane Protein-Detoxified Lipooligosaccharide
Vaccine in Liposomes
J. Babcock1, J. Berman2, B. L. Brandt3, E. E. Moran3, N. M. Wassef4, C. R. Alving4,
W. D. Zollinger3
1Department of Clinical Trials, Walter Reed Army Institute of Research (WRAIR),
Silver Spring, MD, 2Department of Biology, WRAIR, Silver Spring, MD, 3Department
of Bacterial Diseases, WRAIR, Silver Spring, MD, 4Department of Membrane Biochemistry,
WRAIR, Silver Spring, MD
P11 Liposomal P6 Vaccination Induces Passive Protection Against Non-typeable Haemophilus
influenzae (NTHi) in Weanling Rats
A. Rosenthal1, W. A. Ernst2, J. P. Adler-Moore1
1California State Polytechnic University, Pomona, CA, 2Molecuar Express, Inc.,
Los Angeles, CA
30
on Vaccine Research
FINAL PROGRAM
P12 Shigella Invaplex Enhances Cellular and Humoral Immune Responses to Campylobacter FlaA
Protein: Potential for Enteric Combination Vaccine
R. W. Kaminski1, L. F. Lee2, K. R. Turbyfill1, D. Scott2, P. Guerry2, E. V. Oaks1
1WRAIR, Silver Spring, MD, 2Naval Medical Research Center, Silver Spring, MD
P13 Activax®: Towards the Development of a Multivalent Oral Vaccine for Travelers’ Diarrhea
G. S. Nabors, P. W. Hinds, II, R. Kango
Antex Biologics, Gaithersburg, MD
P14 Lactococcal Ghosts as Carrier in S. Pneumoniae Mucosal Subunit Vaccines
K. Leenhouts1, P. Adrian2, M. van Roosmalen1, R. Kanninga1, S. Estafao2, A. Steen3,
G. Buist3, J. Kok3, O. Kuipers3, R. de Groot2, G. Robillard1, P. Hermans2
1BioMaDe Technology Foundation, Groningen, NETHERLANDS, 2Department of
Pediatric Infectious Diseases, Erasmus University Rotterdam, Rotterdam,
NETHERLANDS, 3Department of Molecular Genetics, State University Groningen,
Groningen, NETHERLANDS
Poster Group 3:
HIV Vaccine Development
P15 Developing an Immunogenic Consensus Sequence T cell Epitopes for the GAIA Cross-Clade
HIV Vaccine
A.S. De Groot1, H. Sbai2, E. A. Bishop2, S. Foti2, J. Franco2, M. Lally3,
D. B. Weiner4, K. H. Mayer3, C. C. J. Carpenter3, W. Martin5
1Department of Community Health, Brown University, EpiVax, Inc, Providence, RI,
2Department of Community Health, Brown University, Providence, RI, 3Immunology
Center, Miriam Hospital, Providence, RI, 4University of Pennsylvania School of Medicine,
Philadelphia, PA, 5EpiVax, Inc, Providence, RI.
P16 Induction of high levels of HIV-Gag expression and anti-Gag immune response elicited by
lysosomal associated membrane protein (LAMP) luminal domain in LAMP/Gag DNA vaccine
chimeras
L. B. Arruda, P. R. Chikhlikar, M. Maciel Jr., J. Thomas August, E. T. A. Marques Jr.
Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore,
MD.
Poster Group 4:
Vaccines Against Viruses
P17 Cell-based ELISA for Potency Measurement of FluMistTM – a Live, Attenuated Influenza
Virus Vaccine
K. Sra, J. Xu, J. Reddy, K. Schweighofer, J. Soni, J. Pham, A. Lewis, A. Pan, H. Mehta
Analytical Biochemistry, MedImmune Vaccines, Mountain View, CA.
31
Sixth Annual Conference
FINAL PROGRAM
P18 Comparability of a Manual and Semi-Automated Median Tissue Culture Infective Dose
(TCID50) Assay for the Potency Measurement of FluMistTM -A Live, Attenuated Influenza
Virus Vaccine
A. Pan, J. Reddy, J. Xu, J. Soni, J. Pham, A. Lewis, K. Sra, W. White, I. Cho,
E. Gopinath, H. Mehta
Analytical Biochemistry, MedImmune Vaccines, Inc., Mountain View, CA.
P19 Correlation between influenza vaccine induced cytokine production and change in
CYP3A4 activity
M. S. Hayney1, R. M. Fohl1, D. Muller2
1School
of Pharmacy, University of Wisconsin, Madison, WI, 2Medical School,
University of Wisconsin, Madison, WI.
P20 Epidermal Powder Immunization against Influenza
D. Chen, Q. Chu
PowderJect Vaccines, Madison, WI.
P21 Evaluation of immunity to mumps virus: Comparison of plaque reduction neutralization
assay (PRN) to ELISA
J. P. Mauldin1, K. Carbone1, R. Yolken2, S. Rubin1
1Center for Biologics Evaluation and Research, FDA, Bethesda, MD, 2Department of
Pediatrics, The Johns Hopkins University, Baltimore, MD.
P22 Vaxfectin Enhances Antibody And Cd8+ T Cell Responses To Low Doses
Of Plasmid Encoding A Malaria Antigen
M. Sedegah
Malaria Program, Naval Medical Research Center, Silver Spring, MD.
P23 Development of a mucosal vaccine against RSV
S. Singh, S. Pillai, K. Scissum-Gunn
Department of Biology, Alabama State University, Montgomery, AL.
P24 C3d as a genetic adjuvant for DNA vaccines diverts the immune response against malaria
E. S. Bergmann-Leitner1, S. Scheiblhofer2, R. Weiss2, D. Winter3, E. H. Duncan1,
E. Angov1, F. Khan1, G. Tsokos3, J. Thalhamer2, J. A. Lyon1
1Dept. Immunology, Walter Reed Army Institute of Research, Silver Spring, MD,
2Institute for Biochemistry, University of Salzburg, Salzburg, AUSTRIA, 3Dept. Cellular
Injury, Walter Reed Army Institute of Research, Silver Spring, MD.
32
on Vaccine Research
FINAL PROGRAM
Poster Group 5:
Vaccines for Veterinary Applications
P25 Poxvirus vaccines – the myxoma virus and European rabbit model
M. M. Adams, B. H. van Leeuwen, P. J. Kerr
Pest Animal Control Cooperative Research Centre, CSIRO Sustainable Ecosystems,
Canberra ACT, AUSTRALIA.
P26 Bovine Pulmonary Vascular Disturbances Following Exposure to Vaccine Derived
Mannheimia (Pasteurella) haemolytica Antigens
B. Weekley, P. Eyre, H. Veit, N. Sriranganathan;
College of Veterinary Medicine, Virginia Polytechnic Institute, Blacksburg, VA.
P27 Failure of Antibiotic Treatment in Horses and Effect of Autogenous Vaccines
O. J. Nolte1, H. E. Weiss2
1Department
of Hygiene and Medical Microbiology, Hygiene-Institut, Heidelberg,
Heidelberg, GERMANY
GERMANY,
2CVUA,
Poster Group 6:
Application of Plant-made Vaccines
P28 Immune Response in Chickens Following the Oral Administration of Plant-Expressed
Heat Labile Toxin
S. R. Webb1, T. J. Miller2, M. Fanton2, H. S. Mason3, D. D. Kirk4, C. Artzen4
1Dow AgroSciences, Indianapolis, IN, 2Benchmark Biolabs Inc, Lincoln, NE,
3Department of Plant Biology, Arizona State University, Tempe, AZ, 4Arizona State
University, Tempe, AZ
P29 A Plant-based Mucosal Vaccine For Amebiasis
F. Medina-Bolivar1, V. Funk1, R. Wright1, B. Mann2, S. Stroup2, W. Petri Jr.2,
C. Cramer1
1Department of Plant Pathology, Virginia Tech, Blacksburg, VA, 2Department of Medicine,
University of Virginia Health System, Charlottesville, VA
P30 Efficacy of an Edible, Plant-derived Immunocontraceptive Vaccine in Mice and Voles
A. M. Walmsley1, D. D. Kirk1, L. Rowland2, T. J. Miller3, H. S. Mason1
1Department of Plant Biology, Arizona State University, Tempe, AZ, 2Department of
Natural Resources, Cornell University, Ithaca, NY, 3Benchmark Biolabs, Inc., Lincoln, NE
P31 Expression of a tuberculosis antigen in plants
M. Rigano, D. D. Kirk, L. Alvarez, J. Pinkhasov, Y. Jin, A. M. Walmsley
Department of Plant Biology, Arizona State University, Tempe, AZ
33
Sixth Annual Conference
FINAL PROGRAM
Poster Group 7:
Vaccine Policy and Safety
P32 Childhood Vaccines: Ensuring an Adequate Supply Poses Continuing Challenges
J. L. Major1, L. Y. A. McIver1, T. Saiki1, L. Spangler1, F. Pasquier1, J. Heinrich2
1Health Care, U.S. General Accounting Office, Seattle, WA, 2Health Care, U.S. General
Accounting Office, Washington, DC.
P33 Using the Vaccine Formulary Selection Algorithm for Establishing Economical Value of
New Combination Vaccines
E. A. Medina1, D. A. Allwine1, B. G. Weniger2
1Austral Engineering and Software, Inc., Athens, OH, 2Immunization Safety Branch,
National Immunization Program, Centers for Disease Control and Prevention, Atlanta,
GA.
P34 Analyzing the Economic Value of Combination Vaccines by Reverse Engineering
a Vaccine Selection Algorithm
S. H. Jacobson1, E. C. Sewell2, T. Karnani3
1Department of Mechanical and Industrial, University of Illinois, Urbana, IL,
2Department of Mathematics and Statistics, Southern Illinois University Edwardsville,
Edwardsville, IL, 3Mechanical and Industrial Engineering, University of Illinois,
Urbana, IL.
P35 Coverage and Determinants of Immunization Uptake Following Implementation of a
Universal Infant Hepatitis B Immunization Program in British Columbia, Canada
V. P. Remple1, C. McIntyre1, K. Pielak1, R. White1, W. Wu1, M. Bigham2
1Department of Epidemiology, British Columbia (BC) Centre for Disease Control,
Vancouver, BC, CANADA, 2Canadian Blood Services, Vancouver, BC, CANADA.
P36 Injection site reactions to booster doses of acellular pertussis vaccine: rate, severity and
anticipated impact
K. Pielak1, D. Skowronski1, V. Remple1, J. Macnabb1, D. Patrick1, S. Halperin2,
D. Scheifele3;
1University of British Columbia Centre for Disease Control, Vancouver, BC, CANADA,
2Dalhousie University, Halifax, NS, CANADA, 3BC Children’s Hospital, Vancouver,
BC, CANADA.
P37 Orchitis reported after immunization
V. Pool1, R. Pless2
1Immunization Safety Branch, National Immunization Program/CDC, Atlanta, GA,
2Immunization and Respiratory Infections Division, Health Canada, Ottawa, ON,
CANADA
34
on Vaccine Research
FINAL PROGRAM
P38 A pan-European consortium for the study on autovaccination – A way to combat the most
common pathogens/infectious diseases?
O. J. Nolte, The EURO-ATVo:CARD Consortium
Department of Hygiene and Medical Microbiology, Hygiene-Institut, Heidelberg,
GERMANY
35
Sixth Annual Conference
ABSTRACTS OF
INVITED
PRESENTATIONS
36
on Vaccine Research
ABSTRACTS OF INVITED PRESENTATIONS
1
Vaccination and Immunological Memory
A. Lanzavecchia
Institute for Research in Biomedicine, Bellinzona, SWITZERLAND.
Vaccination acts by inducing immunological memory that protects
from subsequent encounters with pathogens or toxins. Primed
individuals not only can mount secondary immune responses that are
more rapid and effective than primary responses, but also maintain, in
the absence of further boosting, a certain level of effector T cells and
antibodies for a lifetime. These aspects of immunological memory have
a distinct cellular basis. Recall responses are mediated in secondary
lymphoid organs by central memory T cells and memory B cells, while
immediate protection is mediated in peripheral tissues by effector
memory T cells and by antibodies produced by long-lived plasma cells.
I will review the experimental evidence supporting a ìstem cell modelî
of immunological memory. Central memory T cells and memory B
cells are intermediates of a progressive differentiation process, which
have acquired the capacity to proliferate and differentiate in response
to polyclonal stimuli such as cytokines, microbial products or
bystander T cell help. While self renewing, central memory T cells and
memory B cells continuously spill out effector T cells and plasma cells,
thus replenishing those that turn over. I will describe in details the
mechanisms that sustain serum antibody levels following vaccination
and discuss the implications of these findings for vaccine design.
3
NOT AVAILABLE
2
Lessons Learned From the Worldís First Phase III Efficacy Trials of
Candidate HIV/AIDS Vaccines
D.P. Francis
VaxGen, Inc.
Many lessons have been learned while conducting the worldís first
AIDS vaccine efficacy trial. Here are some: 1) although vaccines are well
understood to be the key to controlling epidemic infectious diseases like
AIDS, they do not receive the same social, political, or financial support
as do therapeutic agents; 2) although important questions are not
known before advancing candidate vaccines into clinical trials, if the
need for a vaccine justifies the financial, personal, and scientific risk,
one must move into uncharted waters and let the empiric data provide
the information; 3) although the government and foundations were
reluctant to fund these studies, the private sector, seeing the possibility
of profit, was willing to take the risk; 4) many of the researchers
exploring futuristic vaccine advances have no experience in the real
process of regulated, industrial vaccine development; 5) the experience
from WHO/UNAIDS, CDC and NIH-funded studies proved to be key
in establishing eligibility criteria, developing recruitment materials,
clinic staff expertise, and general study design and conduct; 6) essential
for success in Thailand has been the strong national commitment and
interest of the local government authorities and academic institutions
toward vaccine research. In addition, key advice and support came from
WHO/UNAIDS; 7) building in regular assessments of potential medical
and social harms in the design of the study has enabled us to address
issues quickly and to ensure that the study is not causing the medical
and social harms that were predicted. And now that we have final data,
the lessons are still coming in.
4
Pneumococcal Conjugate Vaccines (PCV) – What is the Risk of
Post-Vaccination Emerging Serotypes and Replacement Diseases?
R. Dagan
Ben-Gurion University, Beer-Sheva, ISRAEL.
Streptococcus pneumoniae (Pnc) resides in the nasopharynx (NP)
and is part of the normal flora. From there, it may spread to cause
mucosal and invasive infections, or spread to other individuals. The
recent development of PCV raises hopes for significant reduction in
both pneumococcal diseases in general and antibiotic-resistant Pnc (RPnc). In efficacy studies, administration of PCV resulted in reduction of
the rate of invasive and mucosal infections caused by the serotypes
included in the PCV (VT) and somewhat by antigenenically-related
serotypes. Furthermore, NP carriage of the VT and VT-related Pnc and
R-Pnc was also reduced, with associated reduction in transmission.
Surprisingly, the reduction of VT and VT-related Pnc was associated
with an increase in carriage and mucosal infection caused by VTunrelated strains (VTNr). The full significance of this phenomenon
termed ìreplacement phenomenonî has not yet been fully elucidated.
There is clear evidence of replacement disease in acute otitis, and
evidence of some replacement disease in invasive infection is
accumulating. Despite this, an overall benefit of the widespread PCV
use in infants in the US (the only country with extensive PCV use) is
obvious, not only in vaccine recipients, but also in adults, especially in
the elderly.
In the next few years, the real significance of replacement
phenomenon must be evaluated, especially in view of some virulent and
antibiotic-resistant VTNr strains. This task is further complicated by the
continuous selection of Pnc and R-Pnc by contact with unvaccinated
populations and continued selective antibiotic pressure.
37
Sixth Annual Conference
ABSTRACTS OF INVITED PRESENTATIONS
5
Unexpected Challenges on the Road to Polio Eradication
S. L. Cochi
National Immunization Program, Centers for Disease Control and Prevention,
Atlanta, GA.
The initiative to eradicate poliomyelitis worldwide, launched in
1988 by the World Health Assembly, has made remarkable progress.
From 1988 through the end of 2002, the number of countries where
polio was endemic decreased from >125 to 7, and the number of polio
cases decreased by >99% from an estimated 350,000 in 1988 to 1,915
reported in 2002 (as of 25 February 2003). Wild poliovirus type 2 has
not been detected worldwide since 1999. Three WHO regions (the
Americas, Western Pacific, and European), comprising more than 3
billion people in 134 countries and territories, have been certified free
of indigenous wild poliovirus. High quality surveillance data are
increasingly guiding the implementation of national programs. Within
the remaining endemic zones, progress is indicated by decreasing
geographic extent of virus transmission and a reduced number of
circulating virus lineages. However, considerable challenges remain to
complete global polio eradication, particularly in the ìhigh
transmissionî areas of northern India, Afghanistan/Pakistan and
Niger/Nigeria, where the quality of supplementary immunization must
be improved, as well as the ìlow transmissionî areas of Egypt and the
Horn of Africa. A resurgence of polio in 2002 in northern India
accounted for 84% of global polio cases. In the post-eradication period,
challenges include management of the risks related to the continued use
of the oral polio vaccine: 1) vaccine-associated paralytic polio (VAPP);
2) the potential for circulating vaccine-derived poliovirus (cVDPV)
outbreaks such as occurred in Hispaniola, the Philippines, and
Madagascar; and 3) rare immunodeficient individuals who are longterm excretors of vaccine-derived polioviruses (iVDPVs).
7
Anthrax Vaccines: Issues and Answers
A. M. Friedlander
US Army Medical Research Institute of Infectious Diseases, Frederick, MD.
Anthrax is a disease of antiquity, associated with the origins of
microbiology, immunology, and vaccinology. The long acknowledged
potential use of Bacillus anthracis, the etiologic agent of anthrax, as a
biological weapon was given credence by revelations during the 1990
Gulf War. This led for the first time in history to vaccinating a
population, not against a naturally occurring disease but against the
threat of using a microorganism to intentionally cause disease. The
cases of anthrax that occurred in the fall of 2001 confirmed our worst
fears and altered the practice of medicine. In this presentation I will
review aspects of the pathogenesis of anthrax as it relates to vaccination
and then discuss the use of the current licensed vaccine, evidence for its
efficacy and research to modify the current regimen and develop new
candidate vaccines.
38
6
Agricultural Bioterrorism: Managing the Threat
M. Wheelis
Department of Microbiology, University of California, Davis, CA.
The agricultural sector is highly vulnerable to economic bioterrorism
because of the ease of attack and the massive economic consequences of
even small outbreaks of some animal diseases. Containing outbreaks of
exotic animal diseases traditionally has relied on culling all potentially
exposed animals, both because vaccines for many of the diseases are
unavailable or not very effective, and because serology is used to
determine the presence of a disease in a country. However, culling is very
wasteful, and magnifies the cost of disease containment. A better
strategy would be to develop effective vaccines and delivery methods for
the potential bioterrorist agents, that would make culling unnecessary,
and would allow vaccinated animals to be distinguished from naturally
infected ones.
8
New Strategies for Safer Smallpox Vaccines
B. S. Graham
Vaccine Research Center, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Bethesda, MD.
The existence of variola stockpiles and the threat of bioterrorism,
have created the need to reinstitute immunization programs against this
deadly and contagious virus. Although smallpox eradication was
successfully achieved using replication-competent vaccinia, this
approach is known to be associated with a small, but finite, incidence of
serious side effects. Modified Vaccinia Ankara (MVA) was derived from
serial passage of vaccinia in chicken embryo fibroblasts. It is not
replication-competent in mammalian cells, and prior studies have
demonstrated safety in humans and immunosuppressed animals.
Clinical trials are now underway to compare vaccinia- and variolaspecific immunogenicity of MVA versus Dryvax (the licensed smallpox
vaccine), and to evaluate the efficacy of MVA against vaccinia
inoculation.
on Vaccine Research
ABSTRACTS OF INVITED PRESENTATIONS
9
South American Arenaviruses: Will They Emerge as Threats?
C. J. Peters
University of Texas Medical Branch, Galveston, TX 77555
Arenaviruses are chronic infections of specific rodents (Family
Murinae and in the Americas sub-family Sigmodontinae). At least four
of the viruses are highly pathogenic for humans and cause the viral
hemorrhagic fever syndrome with high mortality: Junin (Argentine
hemorrhagic fever), Machupo (Bolivian hemorrhagic fever), Guanarito
(Venezuelan hemorrhagic fever), and Sabia (one naturally infected
patient from Brazil). Their distribution is limited by the distribution of
their specific rodent host, the prevalence of infection in the rodent, and
the nature of rodent human contact. Junin virus appeared in a focal
area of the pampas in the 1950ís and gradually extended its range to
include a risk population of millions today; the factors governing its
emergence and spread are unclear. Machupo virus caused sporadic
cases in the early years of settlement in the Beni Department of Bolivia
and then surprised the settlers when its rodent host entered towns and
caused large epidemics; this was controlled by anti-rodent measures but
sporadic cases continue. Guanarito virus welcomed settlers in northern
Venezuela in 1989 and has continued with intermittent activity since.
There are many more partially characterized arenaviruses in the
Americas and almost certainly unknown, uncharacterized arenaviruses
among other rodent species. Thus, we will almost certainly see
emergence of new arenavirus hemorrhagice fevers, either through
poorly understood mechanisms as seen with Junin virus or by the
inexorable encroachment of humans on previously unexploited land
and the clearing of forest to permit the proliferation of high numbers of
savanna rodent species.
11
NOT AVAILABLE
10
Global Trends and Issues in Vaccine Supply
J. B. Milstien
Center for Vaccine Development, University of Maryland School of Medicine,
Montpellier, FRANCE.
The United States has been in a vaccine supply crisis for several
years. The primary factors include major manufacturers leaving the
traditional vaccine market; lack of sufficient capacity investment for
some new vaccines; the ban on thimerosal in vaccines, leading to delays
in supply availability; and the shift in public attention towards
bioterrorism products. Worldwide there also continue to be vaccine
shortages. Similar factors, lack of profitability, inadequate demand
forecasting, and a shifting vaccine market, come into play. The
international traditional market niche is now dominated by large
developing country suppliers, while those multinational companies still
in the global vaccine market are mostly focusing on newer higher profit
products. There is a divergence in products between the industrialized
and the developing world, a situation of concern for future availability
of these products. Finally, demand forecasting has not been realistic,
with vaccine uptake well below need in many developing countries.
Several initiatives of the international public health community are
addressing these issues: the Global Alliance for Vaccines and
Immunization with its linked Vaccine Fund assists in planning,
financing, and procurement, especially for newer products; a new
collaborative Vaccine Provision Project of UNICEF, WHO and the
Vaccine Fund, is strengthening vaccine forecasting and supply planning
in a project management approach, and vaccine innovation is being
supported in a structured way through GAVIís Accelerated
Development and Introduction Projects. The impacts of these initiatives
on global supply remain to be seen.
12
Vaccine Supply Crises in the USA 2002: An Industry Perspective
P. R. Paradiso
Scientific Affairs, Wyeth, West Henrietta, NY.
Over the past two years, there have been significant disruptions in
the supply of both pediatric and adult vaccines in the U.S. These
shortages included DTaP and dT, influenza, MMR, varicella and
pneumococcal conjugate vaccines. There were many reasons for the
shortages, including manufacturing and regulatory issues, as well as a
fairly abrupt decision to remove thimerosal from all childhood vaccines.
While there was an unusual convergence of many issues, and as such
could be viewed as something of an aberration, this period also very
clearly pointed to the fragility of an industry that historically suffers
from being undervalued. Vaccine development is a lengthy and
technologically challenging process and requires a long-term
commitment of resources. Manufacturing is complex, especially for
products that are a combination of multiple antigens. As a result, the
time from the start of manufacturing to the release of product can be a
year or more. Therefore, when shortages occur, rebuilding inventory
cannot be accomplished quickly. This complexity, together with the
under valuation of vaccines, has reduced the number of vaccine
manufacturers. It has also impacted the ability to incorporate
redundancy within processes that would help safeguard against
interruptions in supply. While the recent vaccine shortages have largely
been resolved, vaccine supply and the health of the vaccine industry will
not be maintained without an appreciation of the value that vaccines
bring to society and a willingness to pay for that value.
39
Sixth Annual Conference
ABSTRACTS OF INVITED PRESENTATIONS
13
NOT AVAILABLE
14
Regulatory/Suppressor T Cells: An Overview
E. M. Shevach
Lab of Immunology, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Bethesda, MD.
The last decade has seen a resurgence in research on suppressor or
regulatory T cells that mediate peripheral tolerance. Regulatory T cells
can be divided into two major subpopulationsóìnaturally occurringî and
ìinduced.î CD4+CD25+ T cells represent the major population of
naturally occurring suppressor T cells and are capable of inhibiting the
activation of both CD4+ and CD8+ T cells in vitro and in vivo. Their
mechanism of suppression of T cell activation in vitro is unknown, but
is independent of the known secreted or cell membrane-bound
suppressor cytokines (IL-4, IL-10 or TGF(). In vivo, depending on the
nature of the inflammatory response , CD4+CD25+ T cells may
produce suppressor cytokines. Regulatory T cells may also be induced by
exposure of CD4+CD25- T cells to antigen by the oral route or in vitro
by activation with antigen in the presence of suppressor cytokines or
under tolerizing/anergizing conditions. These ìinducedî suppressor cells
primarily mediate their effects in vivo and in vitro by secreting
suppressor cytokines. The relationship between the ìinducedî and
ìnaturally occurringî populations is unclear. The suppressor function of
CD4+CD25+ T cells is regulated by the GITR, a member of the TNF
receptor super-family (TNFRSF18). Interaction of the GITR on resting
CD4+CD25+ T cells with its ligand (GITR-L) results in delivery of a
signal that abrogates suppression. This result strongly suggests that
manipulation of the suppressor activity of both CD4+CD25+ and
ìinducedî regulatory cells is feasible and will represent an important
means to up- or down-regulate suppressor T cell function in vivo for
treatment of autoimmune, neoplastic, and infectious diseases.
15
Regulatory T cells in Viral and Bacterial Infections
K. H. G. Mills
Department of Biochemistry, Trinity College, Dublin, IRELAND.
CD4+ T regulatory (Tr) cells play an important role in the
maintenance of tolerance at mucosal surfaces and in the prevention of
autoimmune diseases. However, we have found that pathogen-specific
IL-10-secreting type 1 regulatory T (Tr1) cells are induced during
infection with certain bacteria and viruses. We have generated Tr1
clones specific for hepatitis C virus from patients chronically infected
with the virus (J Infectious Dis, 185, 720). Furthermore, Tr1 cells
specific for filamentous s haemagglutinin (FHA) of Bordetella pertussis
were induced in the respiratory tract of mice during acute infection
with the bacteria, at a time when local T cell responses were suppressed
(J Exper Med, 195, 221) . These Tr1 clones suppressed IFN-_
product____ ion in vitro by Th1 clones specific for an unrelated
antigen and suppressed B. pertussiss-specific Th1 responses in vivo. We
also demonstrated that dendritic cells modulated by pathogen-derived
molecules, such as FHA or cholera toxin (CT), which promote IL-10
and inhibit IL-12 production, directed the induction of Tr1 cells
(Trends Immunol, 23, 405). Peptide-specific Tr1 cell clones were
generated from mice immunized parenterally or mucosally with foreign
peptides or proteins with FHA or CT as adjuvants. Our findings
demonstrate that it is possible to prime antigen-specific Tr1 cells in vivo
by immunization with the antigen and an appropriate adjuvant and this
may provide a useful approach for the treatment of immune-mediated
diseases. However our findings also have significant implications for the
development of vaccines against infectious diseases, where the
induction of Tr cells may not be desirable, especially if Th1 responses
play a major role in protective immunity.
40
16
Role of CD4+CD25+ regulatory T cells in Leishmania infection
Y. Belkaid
Department of Molecular Immunology, Research Foundation Children’s
Hospital, Cincinnati, OH.
The long term persistence of pathogens in a host that is also able to
maintain strong resistance to re-infection, referred to as concomitant
immunity, is a hallmark of certain infectious diseases, including
tuberculosis and leishmaniasis. We showed that the persistence of
Leishmania major in the skin following healing in resistant C57BL/6
mice is controlled by an endogenous population of CD4+CD25+
regulatory T cells. These cells accumulate in the chronic dermis where
they suppress by both IL-10 dependent and independent mechanisms
the ability of CD4+CD25- effector T cells to completely eliminate the
parasite from the site. The sterilizing immunity that is achieved in mice
lacking IL-10 produced by CD4+CD25+ T cells is followed by the loss
of immunity to re-infection, suggesting that the equilibrium that is
established between effector and regulatory T cells in sites of chronic
infection may reflect both parasite and host survival strategies.
on Vaccine Research
ABSTRACTS OF INVITED PRESENTATIONS
17
A Vaccine against Staphylococcus aureus)
R. S. Daum
Department of Pediatrics, University of Chicago, Chicago, IL.
18
Towards the Development of a Pseudomonas Vaccine
G. B. Pier
Department of Medicine, Harvard Medical School, Boston, MA.
S. aureus, is an important pathogen responsible for a variety of
human and veterinary infectious diseases and toxinoses. Among patients,
a substantial disease burden exists from both community-acquired and
nososcomial infections. Antimicrobial therapy for S. aureus infections
has been a constant clinical challenge with fl-lactamase elaboration,
rapidly increasing prevalence of PBP2í, the enzyme mediating methicillin
resistance and intermediate- and high-level resistance to the glycopeptide
vancomycin. The epidemiology and pathogenesis of the different S.
aureus clinical syndromes varies widely, an observation suggesting that a
single approach to vaccine development and deployment will not likely
suffice to prevent all disease. Thus, any strategy for development or
deployment of a S. aureus vaccine must consider the pathophysiology of
the clinical syndrome targeted for prevention, the likehood of
immunogenicity in the targeted population and that a priori
immunologic upregulation will interfere with pathogenesis and thereby
prevent disease. Approaches to vaccine development include both active
and passive immunization. Strategies have included the use of live and
killed whole cell vaccines, vaccines employing one or more protein
virulence factors as candidate antigens, vaccines intended to elicit
antibody against one or more microbial surface components recognizing
adhesive matrix molecules (so-called MSCRAMMs), and vaccines
intended to elicit antibody against polysaccharides elaborated by S.
aureus in vivo and in vitro, poly-N-succinyl B-1-6 glucosamine (PNSG)
and polysaccharide capsules of S. aureus serotypes 5 and 8. Many of these
strategies are under active development and/or are receiving current
evaluation in animal models of disease and patients. Despite considerable
progress, many questions remain and are the subjects of ongoing
investigation.
High level immunity to Pseudomonas aeruginosa infections is most
efficaciously mediated by antibody to the O-antigen of the
lipopolysaccharide. However, protective epitopes on purified or
conjugated O antigens are highly variable, often not immunodominant
and additionally some chemically related, but immunologically distinct
epitopes can interfere with the immunogenicity of each other when
combined into a multivalent vaccine. Newer approaches for inducing
protective immunity are needed. Live, attenuated P. aeruginosa vaccines
with interruptions in the aromatic amino acid synthesis gene, aroA, were
tested for safety and immunogenicity when delivered by intranasal (IN),
intraperitoneal (IP) and oral routes. They were also evaluated for
protecting mice against pneumonia, eye infection and bacteremia
emanating from gastrointestinal colonization followed by induction of
neutropenia.
The mutation completely attenuates the virulence of the microbe in
mice. IN and IP immunization induces high titers of opsonic serum
antibodies specific for the LPS O antigen and were thus serotype specific.
Responses to oral immunization were more variable. Protection against
pneumonia in both intact (high challenge dose) and neutropenic (low
challenge dose) mice was primarily O-antigen specific, as was protection
against bacteremia. In the eye, protection across LPS serogroups was
evident, indicating tissue-specific effectors of immunity may be operative.
Active immunization was more efficacious than passive therapy with
rabbit antibody raised to the attenuated strains, indicating a potential
contribution from cell-mediated immunity. Conclusions: Live, attenuated
strains of P. aeruginosa hold promise for overcoming earlier problems with
immunogenicity and may induce both humoral and cellular effectors that
can combine to maximize host resistance to infection.
19
20
Update on Respiratory Syncytial Virus Vaccine Development
R. A. Karron
Department of International Health, Johns Hopkins University, Baltimore, MD.
Respiratory Syncytial Virus (RSV) is the most important cause of
viral lower respiratory tract illness (LRI) in infants and children
worldwide. In the United States, it is estimated that approximately
70,000—126,000 infants are hospitalized annually with RSV
pneumonia or bronchiolitis, and that the rate of hospitalization for
bronchiolitis has increased since 1980. Though traditionally regarded as
a pediatric pathogen, RSV can also cause life-threatening pulmonary
disease in bone marrow transplant recipients. The elderly are also at risk
for severe RSV disease, and 14,000-62,000 RSV-associated
hospitalizations of the elderly occur annually in the United States. RSV
is a major nosocomial pathogen on pediatric wards, on transplant units,
and among the institutionalized elderly. In the past decade,
tremendous progress has been made in the development of RSV
vaccines. Currently, two types of candidate vaccines are being evaluated
in clinical trials: subunit vaccines for immunization of the elderly, RSV
seropositive children at high risk for severe RSV disease, and pregnant
women, and live attenuated recombinant vaccines which would be used
primarily for immunization of young infants, and perhaps for
immunization of the elderly. It is possible that combinations of
different types of vaccines might be needed for certain populations.
The potential utility of RSV vaccines in the prevention of serious
nosocomial RSV infection will be discussed.
Development of a Vaccine Against Clostridium difficile
K. L. Kotloff
Department of Pediatrics, University of Maryland School of Medicine,
Baltimore, MD.
Clostridium difficile is a major cause of nosocomial diarrhea,
particularly affecting the elderly and immunocompromised. Although
usually responsive to medical therapy, infection can increase morbidity,
prolong hospitalization, and produce life-threatening colitis. Toxins A
and B are the principal virulence factors. Considerable evidence
supports the role of antitoxic immunity, most notably against toxin A,
in prevention and recovery from C. difficile-associated diarrhea.
Vaccines that induce antitoxic immunity are thus being explored as a
means for protecting high-risk individuals. Promising approaches in
preclinical models include recombinant fusion proteins containing the
nontoxic binding domain of toxin A and delivered mucosally either with
adjuvant or via a live attenuated bacterial vector. In humans, a Phase 1
trial has been completed to evaluate a parenteral vaccine containing C.
difficile toxoids A and B. Thirty healthy adults received four spaced
inoculations on days 1, 8, 30 and 60 with one of three doses of vaccine
(6.25 ug, 25 ug, or 100 ug), with or without alum adjuvant. Vaccination
was generally well-tolerated, with occasional, usually mild, systemic
reactions. The most common local reaction, mild arm pain, was
reported by all recipients of toxoid-alum formulation. Nearly all subjects
developed vigorous serum antibody responses to both toxins, as
measured by IgG ELISA and neutralization of cytotoxicity, whereas 50%
developed fecal IgA increases. Serum antitoxin A IgG ELISA titers in all
vaccinees exceeded the levels that have been associated with protection
in clinical studies. Further development of this vaccine as a prophylactic
or therapeutic agent or for producing C. difficile hyperimmune globulin
is in progress.
41
Sixth Annual Conference
ABSTRACTS OF INVITED PRESENTATIONS
21
NOT AVAILABLE
22
Current Status of Rift Valley Fever Virus Vaccines
J. C. Morrill
Orion Research and Management Services, Gatesville, TX.
Rift Valley fever (RVF), an arthropod-borne viral disease, previously
believed to be confined to sub-Saharan Africa, has emerged as a
potential global disease threat. Recent outbreaks in Yemen and Saudi
Arabia have shown the ease with which the virus may spread beyond the
African continent and have highlighted the threat to vast numbers of
immunologically naÔve humans and animals. Formalin-inactivated
RVF virus vaccines as well as a modified-live vaccine are available for
veterinary use in Africa. The only vaccine currently available for use in
humans is an investigational, formalin-inactivated, lyophilized product
developed by the United States Army to protect at risk employees from
occupational exposure. That vaccine requires an initial series of three
inoculations and periodic booster inoculations to achieve and maintain
adequate immunity. A recently developed, live-attenuated RVF vaccine
has been shown to be safe and immunogenic in ruminants, monkeys,
and a limited number of human volunteers and may prove to be a viable
alternative to the existing formalin-inactivated product. The status of
RVF virus vaccines for veterinary and human use will be discussed.
23
Rabies Vaccines: Past, Present & Future
C. E. Rupprecht
Centers for Disease Control and Prevention, Atlanta, GA.
Rabies is one of the oldest infectious diseases. Despite its age, this
acute, fatal encephalitis persists in global distribution, remaining the
most signifcant viral zoonosis today. The disease is fatal once clinical
signs manifest, but is prevented after exposure by administration of
effective biologicals. During the past century, a revolution in vaccine
development occurred. In the first quarter of the 20th century, vaccines
had progressed little beyond Pasteur’s production in neural tissue. Even
today, in many developing countries, vaccines are produced from brain
tissue. However, adaptation of the virus to tissue culture in the 195060s resulted in a vastly improved product in purity, potency, safety, and
efficacy. Application of vaccine en masse resulted in effective herd
immunity and virtual elimination of canine rabies in developed
countries. When applied promptly after exposure, human prophylaxis
with modern cell culture vaccines virtually assures prevention. Higher
cost of some vaccines has required new schedules and strategies in many
parts of the world, where human mortality may exceed 50,000 cases
and in excess of 4 million exposures. Progress in development of
modified-live, attenuated, and recombinant oral vaccines has led to the
control of rabies among wildlife in Europe and North America.
Extension of oral vaccination to free-ranging dogs may eventually be a
critical adjunct to traditional methods of control. The 21st century
should continue to experience the fruits of biotechnology with the
development of nucleic acid vaccines and biologicals produced in
plants. Disease control in carnivores may advance, but rabies
propagation among bats will continue to demand novel approaches in
vaccine design for decades to come.
42
24
Progress Report on Malaria Vaccines
S.L. Hoffman
Sanaria, Gaithersburg,MD 20878
To develop, license, manufacture and deploy a malaria vaccine
scientific, technical, and economics hurdles must be overcome. The
parasites that cause malaria present formidable scientific and technical
challenges to vaccine developers, and the successful deployment of an
effective vaccine will present enormous economic and human resources
problems. It is my opinion that that there will never be a widely used
malaria vaccine unless the vaccine is developed for either infants and
young children in Africa, or travelers from the developed world to the
developing world. The customer for the first vaccine will be
international donor agencies and developed world governments, and the
customer for the second type of vaccine will be travelers or governments
buying for military personnel. The current status of efforts to develop
such vaccines will be discussed, as will the potential timelines for
licensing and deploying an effective malaria vaccine, and the economics
of such efforts.
on Vaccine Research
ABSTRACTS OF INVITED PRESENTATIONS
25
Immune Correlates of Protection in Malaria
A.V.S. Hill
University of Oxford, United Kingdom
26
Translating the Malaria Genome
D. J. Carucci
Malaria Program, Naval Medical Research Center, Silver Spring, MD.
Development of an effective vaccine against Plasmodium
falciparum malaria represents an urgent priority in global public health.
Individuals in malaria endemic areas naturally acquire substantial
immunity to malaria through years of exposure but the nature of this is
complex and no single immune response appears to be of predominant
importance. Analysis of host immunogenetic susceptibility factors and
prospective studies of immune correlates of protection in malariaexposed populations have provided clues for vaccine design.
Antibodies against particular blood stage antigens and cellular immune
responses against epitopes in pre-erythrocytic antigens of the parasite
have been correlated with resistance to infection or disease. Some but
not all of these findings have now led to phase I / II clinical studies of
new candidate vaccine types. Limitations in the capacity of studies of
natural immunity will be reviewed in the context of their likely utility
in vaccine design. Two major limitations are the low levels of natural
immune response induce by many parasite antigens and the diversity of
immunoassays available to search for correlates. Current vaccine
delivery systems can now induce some response levels far greater that
those engendered by decade of exposure to high malarial endemicity.
An alternative approach is to undertake detailed searches for correlates
of protection with partially effective novel vaccines.
The completion of several Plasmodium genomes holds the promise
of developing new and effective interventions against malaria. However,
the technical challenge faced by genome scientists completing these
genomes may only be exceeded by this lofty promise. Much of what has
been accomplished represents only a foundation for further malaria
research and it is not yet clear how to best translate genomes into drugs
or vaccines. One area that may provide additional insights into the
identification of target antigens is high throughput proteomics. This
technical approach combines high resolution liquid chromatography
with tandem mass spectrometry and has been applied to several key P.
falciparum life cycles stages. Using this method, over 2,500 proteins, or
nearly half of the predicted proteins from P. falciparum were identified
from four parasite stages. The characteristics of these proteins may
provide valuable insights into the identification of new drugs and
vaccine targets to combat malaria.
27
28
Transmission Blocking Vaccines
A. Saul
Malaria Vaccine Development Unit, National Institutes of Health, Rockville, MD.
Mosquitoes become infected with malaria parasites when they ingest
blood infected with sexual stages of the parasite. In the mosquito gut,
these parasites fertilize then undergo a complex cycle of development and
replication. They eventually migrate to the salivary gland and are injected
into people to start a new cycle of malaria infection. Antibodies that
target antigens found on the surface of the mosquito stage parasites can
prevent fertilization or otherwise inhibit parasite development,
preventing infection of the mosquito and thus transmission of malaria
from one person to another. Several antigens from both Plasmodium
falciparum and P. vivax that are potential vaccine candidates have been
identified and the leading antigen, Pvs25, an ookinete antigen from P.
vivax is in a human Phase 1 trial. Other trials are expected in the
foreseeable future. Several of the leading candidate antigens are only
expressed by malaria parasites after they are in the mosquito gut.
Therefore, these may represent the parasiteís ìAchilles heelî as these
antigens have never been under human immune selection for lack of
immunogenicity and antigenic diversity. Vaccines based on these
antigens will be one of the most unusual concept in vaccinology: These
vaccines elicit antibodies against a protein never expressed in humans,
kill parasites in another organism (i.e. the mosquito) and will work
through pure ìherd immunityî effect. Never the less, data from animal
models and computer simulations suggest that these vaccines may
become an important component in malaria control programs for low to
medium endemicity and may play a role in reducing morbidity and
mortality in high transmission areas.
Antigen-Specific Early Primary Responses Modulate
Immunodominance of B Cell Epitopes
K. V. S. Rao
Department of Immunology, International Centre for Genetic Engineering and
Biotechnology, New Delhi, INDIA.
In a humoral response, the antigenicity of individual determinants
on a polypeptide antigen is generally thought to constitute a surface
static property of the antigen. This notion stems from the joint
realization of the plasticity of the preimmune B cell repertoire and the
fact that B cells generally recognize antigens in their native forms.
However, our own results have pointed out that the spectrum of
epitopes recognized in an antigen-specific humoral response constitutes
only a fraction of that which may be anticipated. Our studies have
demonstrated that, subsequent to the initial recognition of antigen,
immunological parameters are soon brought into play to restrict the
range of epitope-specific responses that are retained. The low activation
threshold of naÔve primary B cells ensures that, upon first exposure to
antigen, diverse clonotypes directed against the entire gamut of
accessible determinants are induced into a early primary response. Soon
thereafter, however, a stringent selection process enforces that only those
cells with the highest affinity for antigen are selected for seeding of
germinal centers, and consequent retention in the response.
Importantly, this clonotype selection in the pre-germinal center phase
was also shown to translate into a restriction of epitope-specificities,
thereby defining the epitopes to be recognized in the secondary
response. This restriction in epitope-specificities derived from the fact
that the affinity/avidity of early primary responses to individual
determinants varied widely which, in turn, was dictated by the chemical
composition of the epitope. The mechanisms underlying these processes
will be discussed.
43
Sixth Annual Conference
ABSTRACTS OF INVITED PRESENTATIONS
29
Structural Basis for T and B Cell Epitope Immunodominance
S. J. Landry
Department of Biochemistry, Tulane University Health Sciences Center, New
Orleans, LA.
CD4+ helper T cell epitope immunodominance potentially reduces
the adaptability and protectiveness of immune responses. Unlike CD8+
cytotoxic T cell epitopes, helper T cell epitopes are not accurately
predicted on the basis of antigen primary sequence. We have found that
helper T cell epitopes in a variety of antigens, including HIV envelope
glycoprotein, tend to overlap the carboxy-terminal flank of structurally
disordered antigen segments. This pattern could be explained by two
coupled mechanisms of antigen processing: (1) a tendency for
endoproteolytic nicking to occur in unstructured segments and (2)
preferential presentation of sequences adjacent to the new amino
termini. We are modifying epitope immunodominance in
bacteriophage T4 Hsp10. Like Hsp10s of mycobacteria, T4 Hsp10 has
immunodominant epitopes on the flanks of the functionally important
mobile loop. Variants of T4 Hsp10 with smaller mobile loops were
resistant to proteolytic nicking but otherwise retained the native
structure. Splenocyte proliferative responses to the variants were more
broadly distributed among Hsp10 peptides. B cell responses also shifted
from the mobile loop to other sites on the antigen. Stimulation of a T
cell hybridoma specific for the mobile-loop flank was sensitive to
antigen structure and correlated with the tendency for nicking to occur
in the mobile loop. Whereas, stimulation of a T cell hybridoma specific
for an epitope in the center of the mobile loop was affected only by
deletions that altered the epitope. These studies confirm that antigen
structure directs helper T cell epitope immunodominance and suggest a
method for improving subunit vaccines.
31
Mass Spectrometric Fine Determination of B Cell Epitopes
K. B. Tomer
Department of Laboratory of Structural Biology, National Institute of
Environmental Health Science/National Institutes of Health, Research Triangle
Park, NC.
The precise determination of epitopes is becoming increasingly
important in the development of antibody-based vaccines and/or
therapeutics. There are a number of rapid methods for determining linear
epitopes, but few of these methods are easily applicable to discontinuous
and/or conformation epitopes. To map epitopes on proteins in their native
conformation that are recognized by antibodies, we are using a combination
of epitope excision and/or epitope extraction combined with mass
spectrometric analysis. In epitope excision, the native protein is bound to an
immobilized antibody and the complex is subjected to proteolytic digestion.
The epitope-containing fragment remains bound to the antibody while the
non-epitope containing fragments can be removed. Direct analysis of the
epitope containing fragment affinity-bound to the antibody by matrixassisted laser desorption/ionization (MALDI) yields the mass of the
fragment. Correlation of the observed mass and the protein amino acid
sequence yields the identity of the epitope-containing fragment. Successive
enzymatic digestions of the affinity-bound epitope-containing fragment,
e.g., tryptic digestion followed by aminopeptidase or carboxypeptidase,
leads to fine-mapping of the epitope. For discontinuous epitopes, we have
used differential lysine acetylation and/or arginine derivatization by
hydroxyphenylglyoxal to probe surface accessibility differences between
antibody-bound and unbound antigen. The application of this approach
will be illustrated by the fine determination of epitopes on HIV gp120 and
gp41 recognized by monoclonal antibodies. The fine structure of B cell
epitopes can be determined by the combination of mass spectrometry with
limited proteolysis of antibody-bound antigen using sequential enzymatic
proteolysis with or without differential surface modification of bound and
unbound antigen.
44
30
T Cell Immunodominance and Memory Regulated by CrossReactivity Between Virus-Specific T Cell Responses.
M. Brehm
Department of Pathology, University of Massachusetts Medical School,
Worcester, MA.
Our laboratory has demonstrated unanticipated T cell crossreactivity between unrelated viruses such as LCMV, Pichinde virus (PV),
and vaccinia virus. Cross-reactivity between heterologous viruses has
dramatic consequences for a host, including enhancement of protection
against subsequent virus challenge, induction of immunopathology, and
shaping the T cell memory pool. Here we show that virus crossreactivity also influences the immunodominance of CD8 T cells
generated by viral infections. Acute virus-specific T cell responses (8
days post-infection) were generated by infecting C57BL/6 mice with
LCMV or PV. Mice were considered immune 6 weeks post-infection.
CD8 T cells were quantitated using either an intracellular cytokine assay
or by staining with MHC-tetramers or MHC-IgG dimmers. We have
defined a cross-reactive epitope between LCMV and PV (NP205-212)
that is subdominant for both viruses. In mice whose TCR repertoires
were altered by previous infection with either LCMV or PV, challenge
with the heterologous virus generated an immunodominant response
against the cross-reactive NP205 epitope with a corresponding
reduction in frequencies of T cells specific for the normally dominant,
non-cross-reactive epitopes. The virus-specific memory pool was also
altered after sequential infection with an increased frequency of crossreactive memory T cells and attrition of non-cross-reactive memory T
cells. Our findings indicate that virus infections shape the T cell
repertoire, causing alterations in both primary and memory CD8 T cell
responses elicited by subsequent infections. Thus, the immunodominant
epitopes recognized by a given individualís T cell response may reflect
past exposures to antigens with potential beneficial or detrimental
effects.
on Vaccine Research
ABSTRACTS OF
SUBMITTED
PRESENTATIONS
45
Sixth Annual Conference
ABSTRACTS OF SUBMITTED PRESENTATIONS
S1
Vaccine Production Using Plant Virus Vectors
A.V. Karasev, H. Koprowski
Department of Microbiology and Immunology, Thomas Jefferson
University, Doylestown, PA.
An ideal vaccine should be safe, inexpensive, and given only once,
preferably orally, while providing protection against multiple
pathogens. Edible plants, used as delivery vehicles for vaccine
components fit this hypothetical ideal product perfectly. For the past
10 years we explored edible plants for production of different vaccine
components, suitable for protection against rabies, respiratory
syncytial virus, HIV-1, hepatitis B, and anthrax. The advantage of
transient expression systems based on plant virus vectors are quick
design, high product yield, flexibility in terms of the plant host
species, as well as possibility of production of multiple vaccine
candidates in the same plant. The expression system based on the
tobacco mosaic virus vector, and utilizing fusions with viral capsid
proteins can easily yield up to 800 micrograms of vaccine protein per
1 g of plant (spinach) leaf tissue. Different plant-produced vaccine
components were confirmed to retain their immunogenicity in
animal models. A plant product when given to human volunteers
orally resulted in priming of the antibody responses against rabies.
Plant virus vectors have a great potential for production of vaccines
in plants.
S3
Plant Virus Particle-Based Candidate Vaccine Against Respiratory
Syncytial Virus
V. M. Yusibov1, C. Davidson1, V. Mett1, S. Gilliam2, T. McVetty2, D. Mann2;
1Center for Molecular Biotechnology, Fraunhofer USA, Newark, DE,
2University of Maryland, Baltimore, MD.
Infections with respiratory syncytial virus (RSV) cause nearly
100,000 hospitalizations in the United States annually, resulting in an
estimated expenditure of $300 million per year. The rate of
hospitalization due to RSV infections worldwide is even higher with
mortality rates approaching 5%. Inspite of all the efforts there is no
vaccine against RSV yet. However, development of a vaccine that will
prevent severe RSV infection of the lower respiratory tract that would
significantly decrease hospitalizations is feasible. We are developing a
peptide-based vaccine against RSV using alfalfa mosaic virus (AlMV)based expression vector that enables rapid engineering and production
of highly immunogenic antigens for screening and subsequent low-cost
production. For example, we engineered a 24-mer peptide of the RSV
G protein as a translational fusion with AlMV coat protein, produced
recombinant AlMV particles containing this peptide, and tested the
immunogenicity of the particle-based peptide in vivo in mice and
cynomolgous macaques, and in vitro in human dendritic cells.
Significant pathogen-specific immune responses were generated in all
three systems: i) mice immunized with the recombinant particles were
protected against challenge; ii) human dendritic cells armed with an
AlMV-RSV-G peptide generated vigorous CD4+ T cell responses in 4
of 5 and CD8+ T cell responses in 3 of 5 individuals tested; and iii)
cynomolgous macaques that received recombinant AlMV particles
responded by mounting strong immune responses. We believe this
approach may validate the potential use of a novel RSV vaccine delivery
vehicle in humans.
46
S2
Expression of Foot and Mouth Disease Viral Antigens in Transgenic
Alfalfa Plants
A. Wigdorovitz
Virology Department, National Institute of Agriculture, Buenos Aires,
ARGENTINA.
The aim of this work was the expression of foot and mouth disease virus
(FMDV) antigens in transgenic alfalfa plants for the production of
experimental vaccines to be evaluated in a murine model. Here, we
report the production of transgenic alfalfa plants expressing a highly
immunogenic epitope from VP1, the complete VP1 protein and the
precursor of the structural proteins of the viral capsid. VP1 expressed in
transgenic alfalfa induced a specific protective antibody response when
parenterally or orally administered to mice. Nevertheless, the
concentration of the expressed protein in the plant tissues was relatively
poor. In order to increase the expression levels of the foreign protein, we
have developed a methodology based on the construction of a fusion
protein composed of a reporter gene, glucuronidase (gus A), fused to
amino acid residues 135 to 160 from VP1. Plants expressing the highest
levels of the immunogenic epitope VP135-160, were efficiently selected
based on their levels of ßGUS enzymatic activity. VP135-160 expressed
in plants was highly immunogenic in mice which developed, a
protective antibody response against virulent FMDV in experimental
hosts. We also expressed the precursor (P1) for the four structural
proteins (VP1, 2, 3 and 4) and the protease 3C of FMDV. The presence
of FMDV empty-like particles in leaf tissues of the transgenic plants was
detected by electronmicroscopy. Parenterally immunized mice developed
a strong antibody response against VP135-160, purified FMDV
particles and the native viral structural proteins. Additionally, these mice
were complete protected against experimental challenge with the
virulent virus.
S4
Immunogenicity of a Recombinant Bacterial Antigen Delivered In
Transgenic Corn
C. O. Tacket1, J. D. Clements2, S. S. Wasserman1, S. J. Streatfield3;
1Center for Vaccine Development, University of Maryland School of Medicine,
Baltimore, MD, 2Microbiology & Immunology, Tulane University School of
Medicine, New Orleans, LA, 3Molecular Biology, Prodigene, College Station, TX.
A number of vectors for oral delivery of foreign antigens have been
tested in animals and humans for safety and immunogenicity. One food
plant delivery system is transgenic corn expressing the B subunit of E.
coli enterotoxin (LT-B). The purpose of this double-blind, placebocontrolled study was to determine whether serum and/or mucosal
immune responses could be generated in volunteers who ingested
transgenic defatted corn germ meal engineered to express LT-B.
Thirteen adult volunteers were randomized in a double-blind manner to
receive on days 0, 7, and 21 either (i) 2.1 gm of defatted LT-B corn germ
meal made from transgenic corn, containing 1 mg of LT-B (n=9) or (ii)
2.1 gm of control defatted corn germ meal (n=4). The corn germ meal
vaccine was well tolerated and easy to administer. Seven (78%) of 9
volunteers developed anti-LT IgA and IgG antibody secreting cell (ASC)
responses usually after the first or second dose. Serum anti-LT IgG
responses also occurred in 7 (78%) of 9 volunteers, usually after the
second dose. Only one volunteer did not respond with either ASC or
serum antibody. As a prototype transgenic plant vaccine, this defatted
corn germ meal vaccine was safe and stimulated both serum and
mucosal immune responses in healthy adults.
on Vaccine Research
ABSTRACTS OF SUBMITTED PRESENTATIONS
S5
Clinical Response in Chickens Following the Administration of
Plant-Made Vaccine Against Newcastle Disease Virus
T. J. Miller1, M. Fanton1, G. Cardineau2, H. S. Mason3, C. Artzen3;
1Benchmark Biolabs Inc, Lincoln, NE, 2Dow AgroSciences LLC, Indianapolis,
IN, 3Arizona State University, Tempe, AZ.
Plant-made vaccines offer a number of benefits when compared to
existing antigen manufacturing technologies including; elimination of
the cold chain, product stability, and improved safety. The objective of
these studies was to determine if plant-made antigens were
immunologically similar to the native antigen, and if the plant-made
antigen could protect animals in a disease challenge. The model antigen
used for these studies was the HN protein from the Newcastle disease
virus (NDV). The HN protein was expressed in NT-1 tobacco cell
cultures and the biochemical characteristics were similar to the native
HN antigen. The serological response in poultry to the plant-made HN
was compared to birds immunized with killed NDV. Similarly,
antiserum from plant-made and native virus HN was able to inhibit
heamagglutination by NDV. A Texas GB disease challenge was
conducted on poultry immunized with plant-made HN and at all doses
tested the birds survived challenge comparable to the killed NDV
controls.
S7
Comparison of Three Assays Used for T Cell Epitope Mapping in
Ebola Virus: IFN-γγ Enzyme-linked Immunospot (ELISpot), IFN-γγ
Intracellular Cytokine Staining, and 51Cr-release.
M. A. Bailey;
Department of Virology, United States Army Medical Research Institute of
Infectious Diseases, Fort Detrick, MD.
Developing a vaccine against an infectious disease relies on detailed
knowledge of the host organism’s immune response to the pathogen. In
the case of Ebola virus a cellular immune response, specifically a
cytotoxic T lymphocyte (CTL) response, is critical for protection.
Characterizing, inducing, and accurately monitoring this response will
be crucial for developing an effective human-use Ebola vaccine.
Mapping Ebola-specific CTL epitopes is the first step in this process. In
our study we compared three highly reproducible, highly sensitive
assays that can be used in conjunction for quick and accurate epitope
mapping. Pools of overlapping 15mer peptides were screened using the
IFN-g intracellular cytokine staining (ICS) assay in C57BL/6, and
BALB/c mice vaccinated with Venezuelan equine encephalitis (VEE)
replicons expressing the Ebola NP, GP, vP24, vP30, vP35, or vP40
genes. Once individual IFN-g inducing epitopes were defined with this
assay, IFN-g ELISpot, and 51Cr -release assays were used to further
characterize the responses, and to compare the assays for accuracy and
reproducibility. We found that the IFN-g assays were highly
reproducible, and usually predictive of cytolyc activity in the 51Crrelease assay.
S6
Model Production of a Potent Plant-Made Vaccine
D. D. Kirk, W. Vonhof, J. Eibner, H. Mason, X. Zhang;
Boyce Thompson Institute for Plant Research, Ithaca, NY.
Use of transgenic plants as an alternative production system holds
significant promise in the push for oral, ambient-stable, subunit
vaccines. Our research group has engineered and manufactured clinical
raw potato vaccine batches for three previous human clinical trials,
conducted in the US. In each case, the basic proof of principal was
achieved however practical demonstration of a realistic potential method
of mass application had not been accomplished. Use of an alternative
production system (tomato) has provided improved consistency in
antigen concentration, and a model system for contained-environment
pharmaceutical production on a moderate scale. Integration of food
processing techniques has facilitated new protocols for consistent
material processing which results in a dry and ambient-stable material
with maximum antigen retention and oral activity. Final plant-derived
vaccine materials are amenable to dry formulation, and provide for
adequate QC sampling on a batch manufacturing basis. The combined
improvements have yielded a feasible plant-made prototype system,
which has been fully evaluated in mice model feeding trials. A prototype
vaccine for Norwalk Virus, tested in mice feeding trials has
demonstrated 100-fold improved potency (both humoral and systemic
immunogenicity) and 10-fold reduction in dose variability compared to
plant-made materials previously administered in human clinical trial.
S8
Intranasal Proteosome™-based F1V Vaccine Elicits Respiratory and
Serum Antibody Responses and Protects Mice Against Lethal
Aerosolized Plague Infection.
T. Jones1, J. Adamovicz2, J. Anderson2, C. Bolt2, D. Burt1, M. Pitt2,
G. Lowell1
1ID Biomedical Corp of Quebec, Montreal, PQ, CANADA,2US Army Medical
Research Institute of Infectious Disease (USAMRIID), Ft Detrick, MD.
Vaccination against pneumonic plague, caused by aerosolized Yersinia
pestis, is a prime anti-bioterrorist requirement. F1V is a recombinant fusion
protein of Y. pestis capsular (F1) and virulence-associated (V) proteins.
Alhydrogel-adsorbed F1V, given intramuscularly, protects mice, but is
ineffective in non-human primates against high-dose aerosolized Y. pestis
challenge, perhaps because it fails to induce respiratory immunity. Nasal
Proteosome™-adjuvanted vaccines for other diseases have demonstrated
safety, induction of serum and respiratory immunity and protection in
non-clinical and Phase 2 clinical studies. Lung washes and sera were
collected from mice immunized twice intranasally with F1V alone or F1V
formulated with Proteosome™-based adjuvant IVX908, or
intramuscularly with alhydrogel-adsorbed F1V. Efficacy was evaluated by
challenging mice with 118-200 LD50 of aerosolized Y. pestis. Nasal
immunization with IVX908–adjuvanted F1V elicited high titers of specific
IgA in lungs whereas intranasal F1V alone or intramuscular Alhydrogeladsorbed F1V did not. Intranasal F1V with IVX908 also induced high
serum titers of specific IgG, comparable to those induced by intramuscular
Alhydrogel-adsorbed F1V. Furthermore, IVX908–adjuvanted F1V
protected 100% against aerosol challenge with 118 LD50 of Y. pestis and
80% against 200 LD50. Nasal immunization with F1V formulated with
the ProteosomeTM-based adjuvant IVX908 induces strong respiratory and
serum antibody responses, and protection against aerosol challenge in a
Pneumonic Plague mouse model. Nasal ProteosomeTM-based F1V
vaccines warrant efficacy evaluation in non-human primates.
47
Sixth Annual Conference
ABSTRACTS OF SUBMITTED PRESENTATIONS
S9
Evaluation of a Genetically Modified Live Attenuated Vaccine for
Venezuelan Equine Encephalitis.
D. S. Reed1, M. Hart2, W. Pratt2, C. Lind2, P. Gallagher1, M. Lackemeyer1,
M. Parker2;
1Department of Aerobiology, USAMRIID, Frederick, MD, 2Department of
Virology, USAMRIID, Frederick, MD.
Venezuelan equine encephalitis (VEE) viruses are a group of small,
positive-stranded RNA viruses endemic to Central and South America.
Naturally transmitted by mosquitoes, VEE viruses are highly infectious
by aerosol and are listed as Category B pathogens. In humans, infection
with VEE viruses causes a rapid-onset, febrile, incapacitating illness.
Patients can go on to develop encephalitis although the infection is
rarely fatal. There are currently two vaccines that are given to
laboratory personnel who work with VEE viruses, but there are
concerns regarding the reactogenicity, immunogenicity and efficacy of
these vaccines. New vaccine candidates have been generated by sitedirected mutagenesis of infectious clones generated from virulent
strains of VEE. One candidate, V3526, induced long-lasting immunity
and protection in mice against both aerosol and subcutaneous challenge
with three varieties of VEE (IA, IE, and IIIA). V3526 was subsequently
advanced into studies in nonhuman primates. Six to 8 weeks after
vaccination, nonhuman primates were challenged by aerosol exposure
to VEE viruses of the IA, IE, or IIIA varieties. Analysis of fever,
lymphopenia and viremia postexposure indicated that V3526vaccinated nonhuman primates were significantly protected against
aerosol exposure to VEE viruses. These results demonstrated that
candidate VEE vaccines can protect against aerosol exposure to VEE
and that cross-protection against multiple subtypes can be generated
with one vaccine.
S11
Efficacy of an Oral, Inactivated Whole-Cell Enterotoxigenic E. coli/
Cholera Toxin B Subunit Vaccine in Egyptian Infants
S. Savarino1, R. Abu-Elyazeed2, M. Rao3, R. Frenck2, I. Abdel-Messih2,
E. Hall1, S. Putnam2, H. El-Mohamady2, T. Wierzba2, B. Pittner2, K. Kamal2,
P. Moyer3, B. Morsy4, A. Svennerholm5, Y. Lee3, J. Clemens6;
1Naval Medical Research Center, Silver Spring, MD, 2Naval Medical Research
Unit-3, Cairo, EGYPT, 3National Institute of Child Health and Human
Development, Bethesda, MD, 4Ministry of Health, Cairo, EGYPT, 5University
Goteborg, Goteborg, SWEDEN, 6International Vaccine Institute, Seoul,
REPUBLIC OF KOREA.
Studies in Bangladesh demonstrated protection by cholera toxin B
subunit (CTB) against heat labile enterotoxin (LT)-producing ETEC
diarrhea in older children and adults, but no studies have tested the
efficacy of an ETEC vaccine in high-risk infants and toddlers. We
conducted a randomized, double-blind efficacy trial of an oral,
inactivated ETEC whole cell/CTB vaccine in 6-18 month old Egyptian
children. Subjects received 3 doses of vaccine or killed E. coli K-12
control at two-week intervals and were actively followed for disease for
one year. The primary efficacy outcome was diarrhea associated with
ETEC expressing LT and heat-stable enterotoxin (ST) or ST ETEC
that expressed a vaccine-shared colonization factor (CFA/I, CS1-CS5).
Vaccine efficacy estimates were derived using a Cox proportional
hazards model. Serum titers to CTB and CFA/I were measured preimmunization and 2 weeks after the last dose. 314 subjects received the
complete regimen of vaccine (152) or control (162). During follow-up,
31 and 40 outcomes were observed in the vaccine and control groups,
respectively. The adjusted vaccine efficacy estimate was 20% (95% CI, 29%, 50%). 95% of vaccine recipients exhibited antitoxin
seroconversion, while one-third showed anti-CFA/I seroconversion. In
conclusion, the ETEC/CTB vaccine failed to confer significant
protection against non-severe ETEC diarrhea.
48
S10
Decreased Immunogenicity of Botulinum Pentavalent Toxoid to
Toxins B and E
J. M. Rusnak1, L. Smith2, E. Boudreau1, S. Norris3, T. Cannon4, D. Clizbe1,
M. Kortepeter1;
1Special Immunizations Clinic, USAMRIID, Fort Detrick, MD, 2Department of
Toxinology, USAMRIID, Fort Detrick, MD, 3USAMRIID, Fort Detrick, MD,
4United States Army Medical Information Systems and Services Agency
(USAMISSA), Fort Detrick, MD.
Pentavalent botulinum toxoid (PBT), an investigational
subcutaneous vaccine against toxins A-E, is given at 0, 2, and 12 weeks
with a booster at 12 months. Antibody titers to toxin A are obtained
yearly to assess booster requirements. Antibody titers to toxins B and E
were obtained to evaluate the vaccine’s immunogenicity to these toxins.
Antibody titers were obtained from 158 PBT recipients to toxins B and
E (Jan 1999-Dec 2001), and from 207 vaccinees to toxin A (2001-2).
Titers 28±7 days post primary series were detectable in 24/26, 4/5, and
1/5 vaccinees to toxins A, B, and E. Titers obtained 28±7 days, 6-12
months, and 12-24 months after the last booster were above a titer used
to determine whether a booster was recommended in 47/49(96%),
28/37(76%), and 7/12(58%) vaccinees to toxin A; 8/11(73%),
7/24(29%), and 3/25(12%) to toxin B; and 5/11(45%), 3/24(12%),
and 2/25(8%) to toxin E, respectively. A higher percentage/prevalence of
titers above the pre-determined cutoff was observed if the last booster
was >4 years ago, for toxins B 20/49(41%) and E 12/49(24%). The
decreased prevalence and duration of titers against toxins B and E titers
is consistent with recent vaccine potency studies demonstrating a decline
in vaccine potency to toxin B and failed potency to toxin E, possibly
related to PBT age.
S12
Expected but Unusual Rashes in Adults After First Vaccinia
Vaccination
R. N. Greenberg1, B. A. Plummer1, S. A. Roberts1, M. A. Caldwell1, D. L.
Hargis1, R. J. Hopkins2;
1Department of Medicine, University of Kentucky, Lexington, KY, 2Dynport
Vaccine Company, LLC, Frederick, MD.
CCSV is a vaccinia vaccine utilizing a New York City Board of
Health strain and grown in MRC-5 cells. Data and photographs were
collected post vaccination in 350 adult volunteers. 100 received Dryvax
and 250 received CCSV. Post vaccination rashes occurred in 2
individuals who received Dryvax (2%) and in 6 individuals who received
CCSV (2.4%). The rashes were first noticed 9 to 18 days after
vaccination. All were resolving within 5 days. Rashes were associated
with tingling sensations in hands, pruritis and occasional headache. No
volunteer had fever and all were previously vaccine naive. Antihistamine
treatment reduced pruritis and headache responded to acetaminophen.
No secondary infections occurred. Characterization of the rashes were:
Six volunteers had hundreds of 2-4 mm macular papular (mp) lesions
over the body, including 2 with face and/or scalp lesions. Some lesions
coalesced into red areas with a diameter over 10 cm. Rash intensity
could be severe. One also had a 9X6.5 cm scaly red circumscribed area
suggesting fungal skin infection. Woods light and KOH testing were
negative. Two individuals had mp lesions in a hand-foot and around the
mouth distribution. Swelling occurred around lips and in fingers and
toes. MP rashes are an alarming event after vaccination. Rashes start to
resolve within 5 days and symptoms respond to antihistamine
treatment. Presentations include a “measles-like” rash, “ring worm”, and
a “hand-foot-mouth type” rash.
on Vaccine Research
ABSTRACTS OF SUBMITTED PRESENTATIONS
S13
α, MIP-3α
α, and MIP-3β
β on the
The Adjuvant Effects of MIP-1α
Induction of Gag-Specific Immunity with HIV-1 DNA Vaccine
R. Song1, S. Liu2, J. Wen2, K. W. Leong2;
1Department of Pharmacology, Johns Hopkins University, Baltimore, MD,
2Department of Biomedical Engineering, Johns Hopkins University,
Baltimore, MD.
S14
Differences in Conformation and Epitope Exposure Between
Neutralization Resistant Primary and Neutralization Sensitive
T Cell Line Adapted HIV-1
M. Leavitt1, P. Bouma1, C. Broder1, D. Dimitrov2, J. Robinson3,
S. Zolla-Pazner3, G. Quinnan1;
1Uniformed Services University of the Health Sciences, Bethesda, MD,
2National Cancer Institute, Frederick, MD, 3Tulane University Medical Center,
New Orleans, LA, 4Veterans Affairs Medical Center, New York, NY.
We hypothesize that cotransfection with MIP constructs may induce
recruitment of DCs to capture the HIV-1 DNA vaccine and enhance
CD8+ T cell responses. In our studies, MIP-1a, MIP-3a, and MIP-3b
were cloned and their in vitro expression was measured. The chemotactic
activity on DCs was confirmed. Inflammatory cell filtration was observed
after the inoculation of the chemokine constructs. Finally, chemokine
plasmids were cotransfered into BALB/c mice with pGag to investigate
their roles in modulating the direction and potency of the HIV-1-specific
immunity. We observed that MIP-1a and MIP-3a were potent activators
of Gag-specific CTLs, with an 60% lysis of target cells when MIP-3a
construct was cotransfered with pGag, and the enhanced CTLs were
supported by ELISPOT assay, intracellular IFN-g staining experiment,
and increased expression of IFN-g. On the contrary, dramatic decrease of
Gag-specific IgG was observed. Therefore, MIP-1a and MIP-3a shifted
the responses towards Th1-type immunity. Furthermore, to assess
whether vaccination with pGag plus MIP constructs would protect
against challenge with recombinant vaccinia virus expressing Gag,
unvaccinated and pre-vaccinated animals were challenged with vacciniaGag virus. The strongest protection was observed in animals immunized
with pMIP-3a and pGag, with an 1,300-fold of reduction in virus PFU.
PMIP-1a plus pGag also resulted in a strong protection. Taken together,
our studies demonstrated that co-administration of chemokines with
DNA vaccines offers an important strategy to modulate the nature and
potency of HIV-1 antigen-specific immunity.
We have studied differential epitope exposure on the neutralizationsensitive, low-infectivity, T cell line adapted HIV-1 MN strain (MNTCLA) and the neutralization resistant, primary MN strain (MN-P).
Despite having much greater neutralizing activity against MN-TCLA
than MN-P, a number of MAbs against gp120 epitopes (V3 loop and
CD4-binding site) bound equally well to both Envs. However, there was
greater binding of some MAbs against CD4-induced (CD4i) epitopes to
MN-P, and the binding was modulated by mutations in or near the
coreceptor- and CD4-binding sites. Prior binding of sCD4 similarly
enhanced CD4i epitope exposure in the two clones. MAb 2G12
neutralized and bound to MN-P, but not to MN-TCLA, these
differences were due to conformational effects of mutations and a
possible epitope site mutation, 372 Q/P. Fab (X5) bound and
neutralized MN-P and MN-TCLA with equal efficiency. MAbs against
gp41 epitope clusters I and IV bound MN-TCLA more than MN-P,
while MAbs against gp41 clusters II and III did not display differential
binding characteristics. The results demonstrate that these primary and
TCLA Envs differ with respect to MAb binding to epitopes on gp120
and gp41. The differential binding and neutralization sensitivity of
primary and TCLA Envs may reflect essential differences in the physical
states of the glycoproteins, as well as the availability of epitopes
important for primary virus neutralization and vaccination.
S15
S16
DNA Encoding a HIV-1 Gag/Lysosome-associated Membrane
Protein (LAMP) Chimera Elicits Strong B- and T- Cell Gag-specific
Immune Responses in Rhesus Monkeys.
P. R. Chikhlikar1, L. Barros de Arruda1, M. Maciel Jr1, B. Byrne2,
P. Silvera3, M. Lewis3, E. T.A. Marques1, J. Thomas August1;
1Department of Pharmacology and Molecular Sciences, The Johns Hopkins
University School of Medicine, Baltimore, MD, 2University of Florida,
Gaineszille, FL, 3Infectious Disease Research, Southern Research Institute,
Frederick, MD.
Antigen processing and presentation are crucial steps for development
of immune responses. Antigen access to the MHC II processing and
presentation compartments of antigen presenting cells may be critical for
the development of effective genetic vaccines. We report the development
of an HIV-1 p55Gag DNA vaccine chimera with the Gag gene sequence
incorporated into the cDNA of the human LAMP-1 lysosome-associated
membrane protein (LAMP) between the lumenal and transmembrane
domains. This construct promoted high levels of Rev-independent Gag
protein expression and Gag localization in endosomal compartments colocalized with MHC II molecules. Five rhesus monkeys were injected
three times with a 5mg dose of HIV-1 p55Gag plasmid DNA. The IgG
antibody titers of the immunized monkeys after two immunizations were
1:900, 1:2700, 1:100, 1:900, and 1:2700. In addition, anti-gag specific
IgA was present in three of these animals. T-cell respones by ELISPOT
analyzes of INF gamma secretion were detected in three monkeys after
the second immunization, and after the third immunization four of the
five monkeys presented an average of 380 Gag specific spot forming
cells/per 106 cells. These data further support the critical role of MHC II
targeting for antigen processing and presentation in the function of DNA
vaccines.
Evaluation of a Subunit Vaccine Formulation Containing HSV-2 gD
and IL-12 or MPL in Prophylactic and Therapeutic Guinea Pig
Models of Genital Herpes
J. Strasser1, S. Gangolli2, J. Kowalski2, C. Chaulk1, S. Bhargava2,
A. Abramovitz2, D. Bernstein1, T. Zamb2, D. Long2
1Department of Infectious Diseases, Children’s Hospital Medical Center,
Cincinnati, OH, 2Viral Vaccine Research, Wyeth Research, Pearl River, NY.
Adequate immune stimulation, especially of a Th1-type response,
through vaccine administration, could positively affect the clinical
pattern of recurrent HSV genital disease. This is illustrated by the failure
of subunit vaccines containing adjuvants that induce strong Th2-type
responses. Effective intervention in recurrent disease may be possible
through the use of the immunomodulatory cytokine, IL-12. Here we
report the results of our studies with baculovirus-derived HSV-2
glycoprotein D (rgD) formulated with either monophosphoryl lipid A
(MPL) or IL-12 in the guinea pig model of herpes genital disease. As
expected, prophylactic immunization with rgD, co-administered with
MPL adjuvant, significantly reduced viral shedding, acute and
subsequent recurrent disease symptoms, and viral DNA burden in the
innervating ganglia compared to placebo controls. For therapeutic
vaccination, guinea pigs were inoculated intravaginally with HSV-2,
randomized following acute disease, and immunized on days 14, 28 and
42 post virus challenge. RgD/MPL treated animals with recurrent genital
herpes showed increased HSV-specific antibody levels, but did not
decrease the frequency of clinical recurrences. In contrast, therapeutic
immunization with rgD formulated with recombinant guinea pig IL-12
provided significant protection from recurrent disease symptoms. Our
studies indicate that prophylactic efficacy of rgD immunization is greatly
enhanced by either MPL or IL-12. More interestingly, significant
therapeutic efficacy of rgD is achievable by the addition of IL-12.
49
Sixth Annual Conference
ABSTRACTS OF SUBMITTED PRESENTATIONS
S17
Mucosal Immunization with a Recombinant Chlamydia trachomatis
High Molecular Weight Protein Protects Mice against Heterotypic
Genital Infection
H. Lu, A. M. Harris, G. S. Nabors, W. J. Jackson;
Antex Biologics, Gaithersburg, MD.
S18
An Hsp65-HBV Core Antigen Fusion Protein Primes HBcAg-Specific
CTL Responses in Immunologically Tolerant HBV Transgenic Mice
L. S. D. Anthony1, S. G. Winslow2, H. Liu1, G. Rowse1, B. Wu1,
A. Recktenwald1, J. G. Julander2, L. A. Mizzen1, J. D. Morrey2, M. I. Siegel3
1Stressgen Biotechnologies Corporation, Victoria, BC, CANADA, 2Utah State
University, Logan, UT, 3Stressgen Biotechnologies Inc., Collegeville, PA.
Chlamydia trachomatis is a major causative agent of bacterial
sexually transmitted disease, and infection can lead to pelvic
inflammatory disease, ectopic pregnancy, and infertility. The same
bacteria cause trachoma, which can result in blindness. No vaccine is
available to prevent C. trachomatis infection. We previously reported
that nasal immunization with a highly conserved recombinant high
molecular weight outer membrane protein (rCT110) from C.
trachomatis serovar L2 conferred heterotypic protection against
infertility. Here we report rCT110 confers heterotypic protection not
only against disease but also against vaginal infection. Mice were nasally
immunized on d0, 14 and 21 with rCT110 plus mutant detoxified E.
coli heat labile toxin LT(R192G) as adjuvant. Ten to fourteen days
post-immunization, mice were sacrificed for immunological evaluation
or challenged vaginally with a human serovar E isolate. Immunized
mice had significant spleen cell proliferative responses and exhibited
splenic IFN-g production upon restimulation with rCT110 or UVinactivated elementary bodies. Importantly, genital C. trachomatis
serovar E infections in immunized mice resolved significantly more
rapidly than those in control mice (p < 0.01). Protection was also
achievable via intravaginal, intrapulmonary or subcutaneous
vaccination. These results demonstrate that mucosal immunization
with rCT110 is capable of inducing protective immunity against
heterotypic genital infection. This is the first demonstration of a
recombinant chlamydial protein capable of not only inducing
protective immunity, but also reducing the risk of infertility by C.
trachomatis infection.
In individuals with chronic hepatitis B virus (HBV) infection, viral
persistence is thought to be related to insufficient HBV-specific CTL
responses. Therefore, immunotherapies inducing effective HBV-specific
CTL may promote resolution of infection. Recombinant CoVal™
fusion proteins generated from antigens fused to heat shock proteins
(Hsp) prime potent CTL activity in mice. HspBcor is a CoVal™ fusion
protein engineered from HBV core antigen (HBc) and Hsp65 from
Mycobacterium bovis BCG. Restimulated splenocytes from C57BL/6
mice immunized with HspBcor in buffered saline displayed a high level
of H-2Kb-restricted lytic activity, whereas cells from mice immunized
with HBc antigen alone did not. HspBcor was similarly effective at
eliciting HLA-A2-restricted CTL in HLA-A2Kb transgenic mice.
HspBcor-primed CTL lysed both peptide-pulsed and HBc-transfected
target cells, which express HBc endogenously. IFN-g, a cytokine
implicated in CTL-mediated inhibition of hepatic viral gene expression,
was also released by HspBcor-primed CTL. Induction of CTL was
further evaluated in HBV transgenic mice, which are commonly
employed as a model of chronic HBV infection. A single injection of
HspBcor was observed to elicit CTL in some, but not all, transgenic
mice, which are immunologically tolerant to HBV antigens due to in
utero exposure. These data support the hypothesis that the CoVal™
fusion protein, HspBcor, will be an effective agent in the
immunotherapy of chronic HBV infection.
S19
S20
SIV env gp140 “Domain-Specific” Antibody Responses in Rhesus
Macaques Inoculated with Attenuated SIV/17E: A Novel Strategy
to Understanding Delayed Humoral Immunity
J. L. Rowles, K. S. Cole, M. Murphey-Corb, R. C. Montelaro
Molecular Genetics and Biochemistry, University of Pittsburgh School of
Medicine, Pittsburgh, PA.
Reliable immune correlates of AIDS vaccine protection in the
SIV/monkey model has proven elusive. Qualitative assays of antibody
conformational dependence and avidity previously described a complex
evolution of envelope-specific antibody responses associated with
development of protective immunity in monkeys inoculated with
attenuated SIV strains. The current studies examine the nature of
antibody maturation to attenuated SIV/17E and evaluate potential
immune correlates of vaccine protection based on analyses of antibody
responses to specific envelope domains, designated “domain-specific”
serology. Specific domains of the SIV envelope were substituted into
the HIV-1 envelope background and expressed in the vaccinia system
to produce a novel panel of HIV/SIV chimeric envelope antigens.
Serological assays were done to monitor quantitative and qualitative
progression of antibody responses associated with immune maturation
in monkeys inoculated with an attenuated SIV vaccine. The serological
assays show different levels of antibody responses to individual domains
of the SIV envelope during immune maturation. Qualitative antibody
to these individual envelope domains also varies. These results show
that there is a distinct maturation of antibody responses to individual,
conformational domains of the SIV envelope glycoprotein. “Domainspecific” serological assays reveal new aspects of the antibody
maturation to attenuated SIV vaccines that better characterize the
nature of antibody responses associated with mature, protective
immunity and that provide novel parameters that can be evaluated
further as potential immune correlates of vaccine protection.
50
Benefits of Nontypeable Haemophilus influenzae Vaccines That
Prevent Transmission Compared To Those That Prevent Disease
Given Transmission
J. S. Koopman, X. Lin
Department of Epidemiology, University of Michigan, Ann Arbor, MI.
Vaccines to prevent Nontypeable Haemophilus influenzae (NTHi)
could be developed in ways that have greater effects on pathogenicity
(the fraction of transmissions that result in symptoms) or transmission.
Trials to evaluate vaccines should be designed differently to detect these
different effects. To assess the relative utility of vaccines that reduce the
pathogenicity of infection versus those that prevent infection and/or
reduce transmission from infected individuals who have been
vaccinated, one needs a population model of transmission incorporating
pathogenesis. The data allowing us to construct such a model for NTHi
is minimal. Disparate incidence and prevalence patterns have been
published. A wide variety of different models could be consistent with
the minimal and disparate data available. We examined such a wide
variety of models and found that even the minimal data currently
available is highly informative regarding this issue. Across a broad range
of models and of different parameter values in those models, acute otitis
media incidence in preschool children is much more affected by
naturally acquired immunity affecting transmission than by naturally
acquired immunity affecting pathogenicity. For vaccine programs, this
difference should be even greater. That is because so much otitis occurs
in the 6 to 18 month age group where the direct effects of vaccination
may be difficult to achieve but where indirect effects of vaccination
(prevention of infection by vaccinating others) are stronger.
on Vaccine Research
ABSTRACTS OF SUBMITTED PRESENTATIONS
S21
Safety and Immunogenicity of Two Formulations of a Hexavalent
Diphtheria-tetanus-acellular Pertussis-inactivated PoliovirusHaemophilus influenzae b Conjugate-hepatitis B Vaccine in 15-18
Month-old Children
S. A. Halperin1, J. M. Langley1, T. M. Hesley2, P. S. Zappacosta2,
D. Radley2, A. Hoffenbach3, J. L. Silber4;
1Department of Pediatrics, Dalhousie University, Halifax, NS, CANADA,
2Merck & Co., Inc., West Point, PA, 3Aventis Pasteur, Swiftwater, PA,
4Merck & Co., Inc, West Point, PA.
Combination vaccines decrease the number of injections and improve parental
satisfaction and schedule compliance. In a phase 1, randomized, double-blind, single
center, single dose study, we compared one injection of a licensed pentavalent
diphtheria-tetanus-acellular pertussis-Haemophilus influenzae b conjugate-inactivated
poliovirus vaccine (DTaP-IPV-Hib; Pentacel™; P) to two formulations of a liquid
hexavalent DTaP-IPV-Hib containing hepatitis B vaccine (DTaP-IPV-Hib-HBV) in 90
toddlers 15-18 months of age (mean 17) primed with 3 doses of P. The formulations
contained identical DTaP-IPV components differing only in Hib and HBV (HT=12
µg PRP-T/10 µg HBV; HO=6 µg PRP-OMP/15 µg HBV). Injection site pain,
redness, and swelling were reported by 46.7%, 46.7%, and 20% of P; 43.3%, 43.3%,
and 26.7% of HT, and 66.7%, 46.7%, and 46.7% of HO recipients respectively. Fever
≥ 37.8ºC (axillary) was reported by 3.4% of P, 17.2% of HT and 30% of HO
recipients and irritability by 16.7%, 23.3% and 16.7% respectively.
Vaccine Percent ≥ x / Geometric Mean Antibody Titer 4 to 6 Weeks After
Immunization (x=1.0 µg/mL PRP; 0.1 IU/mL DIP & TET; 4-fold rise PT, FHA,
PRN, FIM; 1:8 Polio 1, 2, 3 NA; *=non-overlapping 95% confidence intervals)
PRP
DIP TET PT
FHA PRN
FIM
Polio1 Polio2 Polio3
µg/mL IU/mL IU/mL EU/mL EU/mL EU/mL EU/mL IU/mL IU/mL IU/mL
P
HT
HO
92.9
19.01
100
40.81*
100
9.36*
100
3.67
100
3.36
100
3.95
100
6.63
100
6.64
100
7.86
100
184.6
100
171.0
96.3
266.2
87.0
228.9
96.0
235.8
77.98
324.4
95.7
154.2
96.0
134.6
92.6
216.6
100
1083
96.0
631.2
88.9
1071
100
615.1
100
384.1
100
285.3
100
466.8
100
424.8
100
757.5
100
70.54
100
91.29
100
65.90
We conclude that the hexavalent formulations appear generally well tolerated and
immunogenic.
S23
Lipopolysaccharide Shigella sonnei Vaccine: from Development to
Clinical Application.
P. G. Aparin1, L. I. Pavlova2, R. P. Chuprinina2, M. E. Golovina1,
S. I. Elkina3, V. I. Shmigol1, T. V. Gantcho3, V. L. L’vov1;
1NRC-Institute of Immunology, Moscow, RUSSIAN FEDERATION, 2National
Institute Biological Standardization MOH, Moscow, RUSSIAN FEDERATION,
3ATV D-TEAM Co., Ltd, Moscow, RUSSIAN FEDERATION.
Low endotoxic, clinically applicable non-denatured
lipopolysaccharides (LPS’s) with high immunogenic potential can be
obtained from endotoxic enterobacteria. New generation LPS is the sole
component (purity >96-97%) of Sh.sonnei vaccine SHIGELLVAC.
Different moieties of LPS molecule - O-polysaccharide, lipid A greatly
influence on host-bacteria interactions (intracellular spread, cytokine
response, degree of inflammation) and acting in synergy for induction of
O-specific adaptive immune response. Efficacy of SHIGELLVAC vaccine
was assessed in Phase III double-blind randomized placebo-controlled
field trials on 3068 volunteers. Efficacy index estimation based on
culture-proven Sh.sonnei cases in vaccinees and placebo group resulted in
92.4% during 6-month period of disease surveillance. Immunization
confers protection of civic population during summer-autumn season
with maximal risk of shigellosis spreading. The preparation was
registered MOH Russia and advised for shigellosis prevention. Vaccine
batches, manufactured in agreement with Pharmacopoeia articles, were
checked for induction of mucosal anti-Shigella immunity in modified
Sereny challenge tests; antigen structure was confirmed by NMRspectroscopy. A strategy of immunization against shigellosis caused by
Sh.sonnei is under development. Immunization in endemic regions, of
risk-groups, and seasonal vaccinations are being considered. Possible
application of LET-LPS’s as vaccine carriers, and anti-shock, anti-cancer
agents, and immunomodulators are the subject of future investigations.
S22
Development of Live Attenuated Shigella Vaccines that Express
Both (ETEC) CFA/I Fimbrial Protein and the B Subunit of HeatLabile Toxin (LT-B).
R. T. Ranallo, F. Cassels, A. Hartman, M. Venkatesan
Department of Enteric Infections, Walter Reed Army Institute of Research,
Silver Spring, MD.
Shigella and Enterotoxigenic Escherichia coli (ETEC) are significant
pathogens that cause severe morbidity in children in developing
countries and are causative agents of diarrhea among deployed military
personnel and travelers. Live attenuated shigella vaccines have been
modified to express ETEC antigens with the goal of constructing
multivalent vaccines that protect against both shigellosis and ETECmediated diarrhea. Recent vaccine candidates for ETEC have focused on
generating both antifimbrial and antitoxin immunity, thus we have
expressed both fimbrial and LT-B in the S. flexneri 2a strain SC608.
SC608 is derived from vaccine strain SC602 and contains deletions in
virG(icsA), iuc and asd. ETEC CFA/I fimbrial chaperone cfaA and the
major subunit cfaB have been cloned in an asd-based plasmid vector
pYA3098. In addition, the cfaB ORF has also been fused to the Cterminus of LT-B using a similar asd vector. Expression of heterologous
proteins in SC608 was verified on western blots of cytoplasmic, surface,
and secreted proteins. Following two intranasal immunizations in guinea
pigs, responses to both shigella LPS as well as to cfaB were observed. In
addition, ELISPOT analysis for ASCs against both LPS and cfaB from
lymph nodes and spleens correlate well with the ELISA results. All
immunized animals were subsequently protected against challenge with
wild-type S. flexneri 2a using the Sereny test. Currently we are
modifying our strains to express simultaneously both cfaB and LT-B.
S24
Mass Vaccination Campaign against Meningococcal C Disease
in the Netherlands
G. P. J. van den Dobbelsteen1, L. van Alphen2, T. F. A. Veerman1,
B. A. M. van der Zeijst1;
1Netherlands Vaccine Institute, Bilthoven, NETHERLANDS, 2Laboratory for
Vaccine Research, Netherlands Vaccine Institute, Bilthoven, NETHERLANDS.
During 2001 a 2.5-fold increase in meningococcal C disease was
observed in the Netherlands. Among a population of 16 million 247
cases contracted the disease (38% of all meningococcal disease). In
January 2002, the Health Council of the Netherlands advised the
Ministry of Health to vaccinate all individuals up to 19 years of age.
The government decided in early spring to vaccinate all individuals
between 1 and 19 years of age with one injection of conjugate vaccine
(Neisvac-C). A nation-wide vaccination campaign was organized. Before
the summer holidays children 14 months to 6 years and 15 to 19 years
were vaccinated by Public Health Communities, after summer the
children in the age group 6-15 years were included. A total of 3.1
million doses were given. The coverage of the campaign was 82% for the
country. An additional 11% was vaccinated by private administration of
vaccine. Meningococcal C disease disappeared in the country since the
vaccination
51
Sixth Annual Conference
ABSTRACTS OF SUBMITTED PRESENTATIONS
S25
Human Bactericidal Antibodies Against Group A Streptococci
(GrAS) Induced by StreptAvax™,a 26-valent M Protein-based
Vaccine.
P. Vink1, J. Dale2, M. Chao-Hong Hu3, M. Reddish3, S. Stroop3, S. McNeil4,
J. Langley4, S. Halperin4, B. Smith4;
1ID Biomedical of Maryland, Baltimore, MD, 2Veterans Affairs Medical Center
& University of Tennessee, Memphis, TN, 3ID Biomedical of Washington,
Bothell, WA, 4Dalhousie University, Halifax, NS, CANADA.
We previously reported that StreptAvax, a 26-valent GrAS vaccine
based on amino-terminal M protein sequences expressed as four
recombinant fusion proteins, was well-tolerated, non-rheumatogenic,
and highly immunogenic in 30 healthy adults. Serotype-specific M
protein antibody titers by ELISA increased by a geometric mean of
12.6-fold (with median four-fold response rate of 84%). Because
bactericidal antibodies supporting opsonophagocytic killing are believed
to be a primary effector of immunity against GrAS, we studied
induction of such antibodies by the vaccine using a modification of
Lancefield’s classic methodology. Significant (p < 0.05) increases in
opsonophagocytic killing in post-immunization sera were demonstrated
for all 26 GrAS vaccine serotypes. For each M serotype, a mean of
51.8% (95% C.I. 46.1 - 57.5%) of subjects without substantial preimmunization killing had 1.0 log2 or greater reduction in GrAS survival
in post-immunization serum compared to pre-immunization serum, and
78.8% (95% C.I. 74.5 - 83.1%) showed some reduction in viable
bacterial counts. In historical context, this is equal or superior to results
reported by Fox et al. using an alum-adsorbed M1.0 M protein vaccine
that proved efficacious against human GrAS challenge (J Clin Invest
52:1885, 1973). Because indirect bactericidal assays using human
phagocytes are cumbersome, we have explored and will describe
potential correlations between ELISA methods and results of the
Lancefield assay.
S27
Induction of T Cell-mediated Immune Responses by HLA Class
II-restricted Naturally Processed Measles Virus Peptides.
I. G. Ovsyannikova, K. L. Johnson, J. E. Ryan, R. C. Howe, D. C.
Muddiman, G. A. Poland;
Vaccine Research Group and the W. M. Keck FT-ICR Mass Spectrometry
Laboratory, Mayo Clinic and Foundation, Rochester, MN.
Identification of immunogenic epitopes (recognized by CD4+ T
lymphocytes) is important for vaccine development. Naturally processed
and presented measles virus (MV) peptides bound to HLADRB1*0301, one of the HLA molecules associated with low measles
antibody levels following immunization, were identified using mass
spectrometry sequencing. Class II peptides were eluted from
immunoaffinity-purified HLA-DRB1*0301 molecules from EBV-B
lymphoblastoid cell line after infection with MV. Two viral peptides
derived from different MV structural proteins, the 19 amino acid
ASDVETAEGGEIHELLRLQ of the phosphoprotein (P) and the 14
amino acid SAGKVSSTLASELG of the MV nucleoprotein (N), were
tested for recognition by T cells from human blood. PBMCs from 350
measles-mumps-rubella-II (Merck) vaccinated subjects (HLA type
unknown, age 12 to 18 years) were cultured alone or with P or N
peptides. As an indicator for T cell-mediated activation, IFN-g levels
from day 6 culture supernatants were quantitated by ELISA. Statistically
significant cytokine responses to MV P peptide were observed in 51 of
307 (17%) PBMCs samples (mean 173.9 pg/ml; range 3.7-927.8
pg/ml), whereas N peptide induced IFN-g in 20 of 341 (6%) subjects
(mean 29.9 pg/ml; range 0.4-129.2 pg/ml). These results show that
endogenously processed MV proteins can be efficiently presented by
class II HLA molecules. Both MV-derived peptides exhibited the
capacity to stimulate viral-specific T cells. These results are promising
for the design of immunization strategies using peptide-based vaccines.
52
S26
Safety and Immunogenicity of a Booster Dose of StaphVAX® , a
Staphylococcus aureus Conjugate Vaccine, in Previously Immunized
Hemodialysis Patients.
A. I. Fattom, S. Fuller, S. Winston, R. Naso, G. Horwith
Department of Research&Development, Nabi Biopharmaceuticals, Rockville,
MD
In a phase III trial, StaphVAX was ~60% effective in preventing S.
aureus in hemodialysis patients over 10 months. A booster dose was
administered to assess safety and immunogenicity. In a cross-over,
double-blind, placebo-controlled trial, 79 patients received a single
booster dose of StaphVAX® and placebo 14 days apart. Safety and
serology were assessed for 6 months. The booster was administered on
average 958 (753 to 1167) days after the first dose. GM type 5 & 8 CP
antibody levels were 73 and 59 µg/mL, respectively. Day 42 after
receiving the StaphVAX® booster GM CP antibody levels were 158
µg/mL and 137µg/mL ( 61%and 57% of post-1st immunization levels)
The response to the booster was not affected by the pre-booster
antibody levels against the carrier protein or specific CP. At six months,
a decline of 20-25% was observed (38-45% post 1st immunization.)
Local and systemic reactogenicity was generally mild to moderate and
transient. Hoemodialysis patients responded to a booster dose of the
vaccine. The vaccination was safe and resulted in increased and more
durable CP-specific antibody levels. This suggests that protection may
be maintained by giving multiple booster injections to patients at
chronic risk. In contrast to what has been observed with pediatric
vaccines, epitopic suppression was not observed in this adult population.
S28
A Measles DNA Vaccine Augmented with IL-2 Protects Infant
Monkeys in the Presence of Neutralizing Antibody
M. F. Premenko-Lanier1, P. Rota2, G. Rhodes1, D. Barouch3, N. Letvin3,
W. Bellini2, M. McChesney1;
1Univeristy of California at Davis, Davis, CA, 2Centers for Disease Control and
Prevention, Atlanta, GA, 3Harvard Medical School, Boston, MA.
A vaccine administered at birth would be instrumental in decreasing
measles morbidity and mortality in developing countries. Maternal
antibodies are effective at neutralizing the live, attenuated measles
vaccine and also interfere with many of the alternative approaches
attempted to date. We have demonstrated that newborn macaques
vaccinated with a measles DNA vaccine consisting of 3 plasmids
encoding the hemagglutinin, fusion and nucleoprotein genes at
100µg/plasmid inoculated intradermally was effective in the presence of
passive antibodies. To improve the immunogenicity of the vaccine, an
IL-2 molecular adjuvant was administered 48 hours post vaccination.
Cellular immunity was detectable in all newborns with passive
antibodies and 4 of 5 without passive antibodies as measured by IFN-g
ELISPOT. Newborns without passive antibodies had significant prechallenge neutralizing antibody titers (p= 0.036; Mann-Whitney Test).
Following challenge with pathogenic MVDavis 87, only 1 of 10 animals
had detectable viremia which was 3 logs lower than controls; the other 9
experimental animals had no detectable viremia. Animals with prechallenge cellular immunity had a significant reduction in viremia
(p=0.011; Fisher’s exact test). When compared to newborns vaccinated
with measles DNA without IL-2, animals vaccinated with IL-2 had a
significant reduction in peak levels of viremia (p= 0.0092, unpaired T
test). This demonstrates that when augmented with IL-2, a measles
DNA vaccine is capable of producing protective immunity in infant
monkeys in the presence of neutrali
on Vaccine Research
ABSTRACTS OF SUBMITTED PRESENTATIONS
S29
Mumps Virus: Changes in Virus Gene Sequence Associated with
Variability in Neurovirulence Phenotype
S. A. Rubin1, G. Amexis1, M. Pletnikov2, K. Chumakov1, K. Carbone1;
1Food and Drug Administration/Center for Biologics Evaluation and Research,
Bethesda, MD, 2Johns Hopkins University, Baltimore, MD.
S30
Rotavirus VP6 Protein Formulated with Polyphosphazene
Adjuvants Induce Protection in a Mouse Challenge Model
A. H. Choi1, J. Chen2, A. K. Andrianov2, M. M. McNeal1, M. Basu1,
R. L. Ward1;
1Division of Infectious Diseases, Cincinnati Children’s Hospital Research
Foundation, Cincinnati, OH, 2Parallel Solutions, Inc., Cambridge, MA.
Mumps virus is highly neurotropic, and prior to widespread
vaccination programs, was the major cause of viral meningitis in the
United States. Mumps virus-associated CNS complications in vaccinees
continue to be reported; outside the U.S., some of these complications
have been attributed to vaccination with insufficiently attenuated
neurovirulent vaccine strains. To examine the genetic basis for mumps
virus neurovirulence we recently developed an in vivo mumps virus
neurovirulence safety test in which the neurovirulence potential of two
mumps virus strains and their neuroadapted and neuroattenuated
variants were assessed. To determine the molecular basis for the
observed differences in neurovirulence and neuroattenuation, the
complete genomes of the two mumps virus strains and their related
variants with variable neurovirulence phenotypes were fully sequenced.
A comparison at the nucleotide level associated three predicted amino
acid changes with enhanced neurovirulence of the neuroadapted
vaccine strain (nucleoprotein PheÆ Pro 468, matrix protein ValÆ Ala
85 and polymerase GluÆ Asp 1165) and associated three predicted
amino acid changes with neuroattenuation of the attenuated wild type
strain (fusion protein ProÆ Thr 91, hemagglutinin-neuraminidase
protein SerÆ Asn 466 and polymerase IleÆ Val 736).
Neuroattenuation was also associated with two nucleotide substitutions
in the 3’ nontranslated region. The potential role of these nucleotide
and amino acid changes in neurotropism, neurovirulence and
neuroattenuation is presented.
We are developing rotavirus vaccines composed of E. coli-expressed
VP6 protein derived from Group A rotaviruses. When VP6 is delivered
intranasally with the enterotoxin LT(R192G) adjuvant, mice are
consistently protected (95% to >99% reduction in fecal shedding relative
to control) against an oral challenge with murine (EDIM) rotavirus.
Safety concerns with enterotoxin adjuvants have led us to evaluate novel
synthetic polyphosphazene adjuvants which have diverse immunostimulating properties. We evaluated PCPP (Adjumer®), PCPP-005,
PCPP-006 and PCPP-0012 polyphosphazene polymers, or LT(R192G)
together with MBP::VP6, a chimera of maltose-binding protein and
EDIM rotavirus VP6 protein. Mice immunized with formulations
containing LT(R192G), Adjumer, PCPP-005, PCPP-006, or PCPP-0012
induced significant (p <0.05) protection (>99, 84, 80, 93 and 54%
reductions, respectively) following EDIM rotavirus challenge. The
protection level in VP6/PCPP-006-immunized mice, which was the
highest among the PCPP variants, was found not significantly lower than
that in mice receiving the LT(R192G) formulation. Interestingly, mice
immunized with VP6 together with any of the PCPP adjuvants, with the
exception of PCPP-0012, generated higher VP6-specific serum IgG,
serum IgA, and fecal IgA responses than LT(R192G), and all
VP6/polyphosphazene formulations induced higher relative titers of
serum IgG1 to IgG2a (30:1 to 130:1) than that induced in
VP6/LT(R192G)-immunized mice (6:1). Thus, these results indicated
that polyphosphazenes have different immunostimulating properties than
LT(R192G) and are promising adjuvants in the formulation of intranasal
VP6 vaccines intended for human consumption.
S31
S32
Intranasal or Oral Immunization of Mice with VP6, a New
Rotavirus Vaccine Candidate, Consistently Protects Mice Against
Viral Shedding after Rotavirus Challenge
R. L. Ward, M. M. McNeal, M. Basu, A. H. C. Choi;
Division of Infectious Diseases, Children’s Hospital Medical Center,
Cincinnati, OH.
We developed a candidate vaccine consisting of an E. coli-expressed
VP6 protein from murine rotavirus strain EDIM. Intranasal (i.n.)
administration to adult BALB/c mice along with the adjuvant
LT(R192G) consistently reduced rotavirus shedding after EDIM
challenge ca. 99%. This study evaluated the robustness of this vaccine
in mice. Inbred or outbred mouse strains were administererd two i.n.
or oral doses (8.8 mg) of either EDIM or human rotavirus CJN VP6
along with 10 mg of LT(R192G). Four weeks later the mice were orally
challenged with murine rotavirus (EDIM or McN) and reductions in
shedding were determined relative to unimmunized mice.
Immunization with EDIM VP6 and adjuvant stimulated 99%
reductions in EDIM shedding in all five strains of inbred mice
examined. Protection against EDIM shedding following i.n.
immunization with CJN VP6 was less (86%; P = 0.02), but still highly
significant. Protection was maintained after i.n. immunization of three
strains of outbred mice with either EDIM or CJN VP6. Protection
stimulated by oral immunization of BALB/c mice with either VP6
protein was not significantly different from i.n. immunization. Finally,
protection after oral or i.n. immunization with EDIM or CJN VP6 was
no different when the mice were challenged with the McN strain.
Mucosal immunization with VP6 and an effective adjuvant consistently
protected mice against rotavirus shedding. Thus, further evaluation of
VP6 as a vaccine candidate is warranted.
Aggregate Content Influences the Type 1:Type 2 Immune Response
to Influenza Vaccine: Evidence from a Mouse Model
D. M. Skowronski1, S. Babiuk2, G. De Serres3, K. Hayglass4,
R. C. Brunham1, L. Babiuk2;
1Epidemiology Services, University of British Columbia Centre for Disease
Control, Vancouver, BC, CANADA, 2Veterinary Infectious Disease Organization,
Saskatoon, SK, CANADA, 3Institut National de Sante Publique de Quebec,
Quebec City, PQ, CANADA, 4Department of Immunology, University of
Manitoba, Winnipeg, MB, CANADA.
During the 2000-2001 season in Canada, an oculo-respiratory
syndrome was detected as an adverse effect to one influenza vaccine.
This vaccine contained a high proportion of unsplit and aggregated
virions. Clinical features were suggestive of type 2 influences on the
immune response. We hypothesized that the implicated vaccine would
induce greater type 2 polarization relative to a non-implicated vaccine
from the same season containing fewer aggregates. Three groups of
eight mice were immunized with the implicated vaccine (Vaccine A),
with non-implicated vaccine (Vaccine B) or not immunized. Sera and
spleen cells were harvested two weeks after secondary immunization.
Influenza specific antibody responses were evaluated. Antigen specific
cellular responses were characterized based on the balance of type 2 (IL4, IL-5) to type 1 (IFN-g) cytokines. Both vaccines induced significant
antibody responses. Immunized animals also expressed more IL-4, IL-5
or IFN-g secreting cells relative to non-immunized mice. Vaccine A
induced significantly more IL-4, IL-5 and IFN-g secreting cells relative
to Vaccine B. Mice immunized with Vaccine A also demonstrated
significantly higher IL-4/IFN-gamma and IL-5/IFN-g ratios relative to
mice immunized with Vaccine B Vaccine aggregates may deviate the
immune response to a greater type 2 cytokine pattern with potential
implications for vaccine screening and safety.
53
Sixth Annual Conference
ABSTRACTS OF SUBMITTED PRESENTATIONS
S33
Risk of Recurrence of Oculo-respiratory Syndrome (ORS)
Associated with Two Different Influenza Vaccines for 2002-2003
G. De Serres1, D. M. Skowronski2, M. Guay3, L. Rochette1, K. Jacobsen4,
T. Fuller4, M. Dionne1, B. Duval1;
1Institut National de Santé Publique du Québec, Beauport, Québec, PQ,
CANADA, 2British Columbia Centre for Disease Control, Vancouver, BC,
CANADA, 3Institut National de Santé Publique du Québec, Longueil,, PQ,
CANADA, 4Westcoast Clinical Research, Coquitlam, BC, CANADA.
This study compares the ORS recurrence risk amongst persons
previously affected in 2000-2001 and/or 2001-2002 when vaccinated
with two different formulations of 2002-2003 influenza vaccine
distributed in Canada. In this randomized double-blind placebo
controlled cross-over study, 147 participants received influenza vaccine
and placebo separated by 7 days. Half received Fluviral (Shire
Biologics) and half received Vaxigrip (Aventis Pasteur). Participants
represented three clinical groups: Group A participants (n=46)
experienced ORS in 2000 and were not revaccinated in 2001, Group B
(n=50) experienced ORS in 2000 and were revaccinated in 2001
(+/- ORS) and Group C (n=51) experienced ORS for the first time
following vaccination in 2001. Telephone interviews assessed
recurrence of ORS. Overall, 25% experienced ORS recurrence
attributable to vaccine. Group A experienced a rate twice as high as
Groups B or C and participants immunized with Fluviral experienced
a rate twice as high as Vaxigrip. In Group B, 33% who experienced
recurrence in 2001 also experienced recurrence in 2002, compared to
25% who had not experienced recurrence in 2001. Most recurrences
were mild; 94% said they would be revaccinated. ORS may occur
following more than one manufacturers’ vaccine but the rate varies by
formulation. Most recurrences are benign and well-tolerated.
S35
Cell Mediated Immune (CMI) Responses to Oral BCG Moreau RdJ
in Healthy Human Volunteers
C. Cosgrove1, L.L.R. Castello-Branco2, R.Giemza1, A. Sexton1,
G.E. Griffin1, D.J.M. Lewis1
1Department of Infectious Disease, St George’s Hospital Medical School,
London, UNITED KINGDOM., 2Fundacao Ataulpho de Paiva/Department of
Clinical Immunology, Fundacao Oswaldo Cruz, Rio de Janeiro, BRASIL
Numerous genetic and phenotypic diverse substrains of BCG exist,
but only BCG Moreau Rio de Janeiro is licensed as an oral vaccine for
human use. Its 70 year safety record makes it attractive for inducing
CMI to recombinant immunogens via mucosal delivery. Fifteen
previously ID vaccinated healthy volunteers received 100 mg
(approximately 3 X107 cfu) BCG Moreau RdJ orally on one occasion,
in a pilot study of immune response kinetics, and in vivo ability to
survive and secrete internal antigens, before evaluating recombinant
oral BCG strains. Oral delivery was well tolerated, with no serious
adverse events, and only transient odoynophagia in six and mild
headache in five subjects. CMI responses: A trafficking proliferative T
cell response was observed in 12/15 subjects, peaking between days 7
and 28. An IFNg immunospot response to secreted internal MPB70
antigen appeared on day 28 and fell by month three. IFNg but not IL-4
secretion of mycobacterial antigen-stimulated PBMCs was detected by
Luminex assay. Humoral responses: As expected, low dose
immunization did not induce humoral responses to PPD or whole
BCG. Low dose oral BCG Moreau RdJ is well tolerated, and induces
TH1-type CMI to somatic and secreted internal mycobacterial
antigens. BCG appear viable in vivo and secrete internal antigens, a
crucial requirement for delivery of recombinant immunogens. Studies
of prime-boost schedules, humoral responses to LAM, and lyophilized
formulations are underway.
54
S34
Original Antigenic Sin and Malaria Subunit Vaccines: The Effect of
Plasmodium yoelii Exposure on Vaccination with 19 kDa
Carboxylterminus of the Merozoite Surface Antigen 1 (MSP119)
and Vice Versa
J. Wipasa1, C. Hirunpetcharat2, A. Stowers3, M. F. Good1, H. Xu1;
1Queensland Institute of Medical Research, Brisbane, AUSTRALIA, 2Mahidol
University, Bangkok, THAILAND, 3National Institutes of Health, Bethesda, MD.
It is well known that exposure to one antigen can modulate the
immune response that develops following exposure to closely related
antigens. It is also known that the composition of the repertoire can be
skewed to favour epitopes shared between a current infection and a
precedent one, a phenomenon referred to as ‘original antigenic sin’. It
was of interest, therefore, to investigate the immunity that develops
following MSP119 vaccination in malaria pre-exposed mice and vice
versa. Groups of mice were infected with P. yoelii followed by treatment
with pyrimethamine (as infection/cure) and then vaccinated with
MSP119; Other groups of mice were immunized with MSP119 and
then subjected to an infection/cure. Pre-exposure of mice to P yoelii
elicited native anti-MSP119 antibody responses, which could be boosted
by MSP119 vaccination. Likewise, infection of MSP119-primed mice
with P. yoelii led to an increase of anti-MSP119 antibodies. However,
this increase was at the expense of antibodies to parasite determinants
other than MSP119. This change in the balance of antibody specificities
significantly affected the ability of mice to withstand a subsequent
infection. These data have particular relevance to the possible outcome
of malaria vaccination for these situations where the vaccine response is
sub-optimal and suggest that suboptimal vaccination may in fact render
the ultimate acquisition of immunity more difficult.
S36
Identification of a Protective 30kDa antigen of Helicobacter pylori
R. G. Keefe, G. S. Nabors, J. Tain, R. I. Walker, Y. Feng, R. Harris,
W. J. Jackson
Antex Biologics, Gaithersburg, MD.
Helicobacter pylori is a pathogen linked to gastric ulcers and stomach
cancer. It is of economic and medical benefit to develop a vaccine to
prevent and treat Helicobacter infection. To discover potentially
protective antigens of H. pylori, we evaluated serological responses in
mice that were protected from infection following vaccination with an
inactivated whole cell H. pylori (HWC) vaccine. C57BL/6 mice were
immunized orally with HWC adjuvanted with mutant detoxified E. coli
heat labile toxin, three times, bi-weekly. Mice were infected, and sera
were used in Western blots to screen H. pylori lysates. Serum from
protected mice revealed a band at 30kDa, which was excised from SDSPAGE gels and sequenced. Based on the N-terminal sequence, the gene
was cloned, and the protein expressed. The gene was found to encode a
protein of 265 amino acids with no homology to any known proteins.
In order to evaluate the protein (HP30) as a vaccine candidate, mice
were vaccinated parenterally with HP30 in both therapeutic and
prophylactic models of H. pylori infection. Serum IgA and IgG, and
gastric CFU and urease levels were measured. HP30 vaccination was
shown to provide protection against infection in the prophylactic
vaccine model, and significantly reduced the stomach bacterial burden
in the therapeutic model. Antibody responses were noted in vaccinated
mice, and lymphocytes from vaccinated animals proliferated in vitro in
response to HP30, indicating both cellular and humoral immune
activation.
on Vaccine Research
ABSTRACTS OF SUBMITTED PRESENTATIONS
S37
Vaccine Immunity to Pathogenic Fungi Overcomes the Requirement
for CD4 Help in Exogenous Antigen Presentation to CD8+ T Cells:
Implications for Vaccine Development in Immune-deficient Hosts
M. Wuethrich1, H. I. Filutowicz1, T. Warner2, G. S. Deepe, Jr.3, B. S. Klein1;
1Department of Pediatrics, University of Wisconsin-Madison, Madison, WI,
2Department of Pathology and Laboratory Medicine, University of WisconsinMadison, Madison, WI, 3Infectious Diseases, University of Cincinnati College
of Medicine, Cincinnati, OH.
S38
Peptide Mimotope of the Polysaccharide Capsule of Cryptococcus
neoformans Identified from an Evolutionary Phage Display Library
R. J. May, D. O. Beenhouwer, M. D. Scharff
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY.
Systemic fungal infections with primary and opportunistic pathogens
have become increasingly common and represent a growing health menace
in patients with AIDS and other immune deficiencies. T-lymphocyte
immunity, in particular the CD4+ Th1 cells, is considered the main
defense against these pathogens, and their absence largely accounts for
increased susceptibility. It would seem illogical then to propose
vaccinating these vulnerable patients against fungal infections. We report
here that CD4+ T cells are dispensable (using wild-type mice depleted of
either CD4+ T cells or mice congenitally deficient for CD4+ T-cells
(CD4-/- and MHC Class II-/-)) for vaccine-induced resistance against
experimental fungal pulmonary infections with two agents, Blastomyces
dermatitidis an extracelllular pathogen, and Histoplasma capsulatum a
facultative intracellular pathogen. In the absence of T-helper cells,
exogenous fungal antigens activated memory CD8+ cells in a MHC classI restricted manner and CD8+ T cell derived cytokines TNF-a, IFN-g and
GM-CSF mediated durable vaccine immunity. CD8+ T-cells could also
rely on alternate mechanisms for robust vaccine immunity, in the absence
of some of these factors. Our results demonstrate an unexpected plasticity
of immunity in compromised hosts at both the cellular and molecular
level and point to the feasibility of developing vaccines against invasive
fungal infections in patients with severe immune deficiencies, including
those with few or no CD4+ T cells.
Cryptococcus neoformans causes life-threatening meningoencephalitis
in a significant percentage of AIDS patients. Mice immunized with a
glycoconjugate vaccine composed of the glucuronoxylomannan (GXM)
component of the cryptococcal capsular polysaccharide conjugated to
TT produce antibodies that can be either protective or non-protective.
Since non-protective antibodies block the efficacy of protective
antibodies, we are interested in developing a vaccine that focuses the
immune response to protective epitopes. Previously, we screened a phage
display library with 2H1, a protective anti-GXM mAb, and isolated
peptide PA1 that had a Kd of 295 nM for 2H1. Mice immunized with
PA1 conjugated to KLH developed high anti-peptide (1:13,000), but
low anti-GXM titers (1:200). We report our efforts to improve this
vaccine by screening a sublibrary with six random amino acids added to
either end of the PA1 motif to identify higher affinity peptides. P206.1,
a peptide isolated from this sublibrary, had 80-fold higher affinity for
2H1 (Kd = 3.7 nM) than PA1. P206.1 bound only protective anti-GXM
antibodies. Mice immunized with P206.1 conjugated to various carriers
did not mount an antibody response to GXM, despite high anti-peptide
titers. However, mice primed with GXM-TT and boosted with P206.1TT developed significant anti-GXM titers (1:180,000). This latter
immunization scheme focused the immune response on protective
epitopes, since only 2-5% of these titers were directed against nonprotective GXM epitopes compared to 20-60% in animals immunized
with GXM-TT. These results have implications for the design of peptide
vaccines to carbohydrate antigens.
S39
S40
Induction of Multispecific Th 1 Type Immunity in Mice Against HCV
by Protein Immunization Using CpG and Montanide ISA 720
R. Wang, Q. Qiu, T. Grandinetti, L. Taylor, H. Alter, J. Shih;
Transfusion Medicine, National Institutes of Health, Bethesda, MD.
Strong, Th1 type cellular immunity against a broad spectrum of
HCV proteins has been shown to be crucial in the resolution of acute
HCV infection. In this study we evaluated the potential of using a
cocktail of HCV core, E1/E2 complex, and full-length NS3 and NS5b
proteins, formulated with CpG oligos and Montanide 720, for the
induction of Th1-type immunity. Groups of mice (n=5) were
intramuscularly immunized once with individual proteins or a
combination of five different HCV proteins. The antibody titers and
isotypes were determined using ELISA. The frequencies of IL-4
secreting and IFN-g secreting cells were assessed by ELISPOT assay.
The means of antibody titers for mice immunized with individual
protein were 102,400, 155,209, 155,209, and 400 for anti-core, antiE1/E2, anti-NS3, and anti-NS5b, respectively. There was no
statistically significant difference in antibody titers and isotype changes
between mice immunized with individual protein and mice immunized
with a cocktail of HCV proteins. The frequencies of IFN-g secreting
cells were significantly higher (ranging form 2 to 10 fold) than that of
IL-4 secreting cells in every group of mice tested. A strong and broad
spectrum of HCV-specific cellular immunity can be raised by
immunization with a cocktail of HCV structural and nonstructural
proteins using CpG oligos and Montanide ISA 720 as adjuvants. This
unique protein immunization method in combination with DNA
immunization strategy should be a valuable approach for HCV vaccine
study in higher animals.
HCV E2 DNA Vaccine with Improved Expression and
Immunogenicity
S. Biswas, S. Lu
University of Massachusettes Medical School, Worcester, MA.
Development of an HCV vaccine remains the most effective
approach to stop the spread of HCV. HCV E2 protein is an important
subunit vaccine candidate due to its potential to neutralize HCV. This
study has been designed to optimize the expression and immunogenicity
of E2 antigen through protein engineering. DNA vaccines were
developed to express different forms of E2 protein: full length or Cterminal truncated forms of E2 with or without an N-terminal human
tissue plasminogen activator (tPA) signal peptide. The levels of in vitro
expression were examined in 293T cells transiently transfected with
these E2 expressing DNA vaccines. Immunogenicity of these constructs
were studied in NZW rabbits using a gene gun and the antiE2 IgG
response was analyzed by ELISA. Expression of the wild type E2 was
mainly intracellular. Removal of the ER retention signal and addition of
a tPA leader (tPA-DE2) led to significantly high level expression of a
secretory form of E2. The tPA leader sequence was important in the
glycosylation and stabilization of E2. DNA vaccine expressing the tPADE2 insert raised the highest titer of anti-E2 IgG responses as compared
to other forms of E2-expressing DNA vaccines. Our study demonstrates
that antigen engineering of HCV E2 protein was effective in improving
the in vitro expression and in vivo immunogenicity of this antigen. This
can lead to more effective E2 DNA vaccine as well as improved
expression of recombinant E2 protein. Both can be used individually or
in combination as a major component in the development of HCV
vaccines.
55
Sixth Annual Conference
ABSTRACTS OF
SUBMITTED POSTER
PRESENTATIONS
56
on Vaccine Research
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P1
Immunological Bioinformatics
O. Lund, C. Lundegaard, P. Worning, M. Nielsen, S. Brunak
Center for Biological Sequence Analysis, Technical University of Denmark,
Lyngby, DENMARK.
New experimental methods such as sequencing, DNA arrays, and
proteomics generate huge amounts of data and there is an ongoing need
to develop new methods for handling these large data sets.
Immunological bioinformatics is the field of applying and developing
bioinformatics tools in the area of immunology. The long term goal of
the research is to establish an in silico immune system. This may be
done in a stepwise fashion where models are developed for components
of the immune system. These models can be combined and may help to
understand diseases, and develop therapies, vaccines and diagnostic
tools for diseases such as HIV, TB, allergy and cancer. A major aim is
to develop methods that can be used to identify epitopes in genomic
data and to select which epitopes should be present in a vaccine.
Current projects include: Development of accurate methods for
predicting peptide binding to Class I and Class II HLA molecules;
Prediction of B cell epitopes; Optimization of plasmids containing
multiple epitopes; Proteasomal cleavage site predictions; and
Epitope/pathogen database construction
P3
The Synthetic Triacyl Pseudodipeptide OM-197-MP-AC Induces
the Maturation of Functional Monocyte-derived Human Dendritic
Cells Able to Induce Primary T Cell Responses
B. Byl1, M. Libin1, J. Bauer2, C. Chiavaroli2, O. Martin3, D. De Wit1,
G. Davies2, M. Goldman1, F. Willems1
1Laboratoire d’Immunologie Expérimentale, Université Libre de Bruxelles,
Bruxelles, BELGIUM, 2R&d, OM PHARMA, Meyrin, SWITZERLAND,
3Institut de Chimie Organique et Analytique, Université d’Orleans,
Orléans, FRANCE.
The capacity of dendritic cells (DC) to activate naïve T cells is
exploited in cellular immunotherapy by reinjecting monocyte-derived
DC carrying an appropriate antigen. For efficient induction of cellular
immune responses mature DC are required. DC were generated in vitro
from monocytes (IL-4/GM-CSF) and cultured 16h with 20 mg/ml
OM-197-MP-AC or 1 mg/ml LPS. Expression of cell-surface markers
was determined by FACS. IL-12(p70) and TNF-a were determined by
ELISA. IFN-g production by naïve CD4+ T lymphocytes after coculture
with autologous mature DC loaded with hepatitis B surface antigen
(HBsAg) was determined by ELISPOT. OM-197-MP-AC upregulated
the expression of HLA-DR, CD40, CD54, CD80, CD83 and CD86 on
the DC surface to a similar extent as LPS. OM-197-MP-AC induced the
release of IL-12(p70) and TNF-a from DC although less strongly than
LPS. DC matured with OM-197-MP-AC induced significantly
(p<0.01) more CD4+ T cells to release IFN-g than immature DC or DC
matured in the absence of antigen. The synthetic triacyl
pseudodipeptide OM-197-MP-AC is able to induce the maturation of
human monocyte-derived DC. These DC are functional in the
stimulation of T cells. These results, together with the low toxicity of
this compound, suggest that OM-197-MP-AC would be useful in
cellular immunotherapy or as an adjuvant for vaccine formulation.
P2
An In-situ Gelling Nasal Vaccine Delivery Platform
Y. Ni1, L. Tian2, K. M. Yates1, I. Tizard2
1DelSite Biotechnologies Inc, Irving, TX, 2Department of Veterinary
Pathobiology, Texas A&M University, College Station, TX.
A unique in-situ gelling nasal vaccine delivery platform is being
developed that potentially overcomes limitations of other delivery
systems. It is based on our GelSiteTM polymer, a unique acidic
polygalacturonan. This polymer, produced under cGMP, possesses
distinct chemical and functional properties. It gels in-situ upon contact
with body fluids. The in-situ gelation and mucoadhesiveness of the
polymerwere examined by histological analysis of nasal cavity following
intranasal delivery to mice. Antigens such as DT-CRM were delivered
intranasally as a solution with or without GelSiteTM polymer. At
various times, serum and lung wash samples were collected. Specific IgG
and IgA antibodies were measured by ELISA. In vitro release
experiments were conducted to evaluate release rates of various antigens.
Gel formation of the GelSite TM polymer was clearly demonstrated in
the nasal cavity. The in-situ gel was mucoadhesive and resided in the
nasal cavity for up to 24 h. Systemic IgG and mucosal IgA responses
increased significantly in the presence of GelSite TM polymer following
single or multiple inoculations. A desired antigen release profile for
different antigens including proteins and viral particles could readily be
obtained by adjusting polymer concentration and other formulation
conditions. The GelSite TM in-situ gelling nasal vaccine delivery
platform significantly increased the systemic and mucosal immune
responses of vaccinated mice. It is highly advantageous in that it 1)
prolongs the antigen nasal residence time and promotes immune
response, 2) provides an easy formulation process, and 3) is suitable for
many different types of antigens.
P4
Efficacy of Adjuvants in Developing Vaccines: Calcium Phosphate
Nanoparticle Vs. Alum – A Comparison
P. R. Nagappan, T. Morcol, A. R. Mitchell, L. Nerenbaum, Q. He, S. J. D. Bell
BioSante Pharmaceuticals, Inc., Smyrna, GA.
Additives in vaccines have vastly improved their safety and
performance. They include preservatives and stabilizers, and adjuvants.
Ideally, adjuvant should be biocompatible, safe and non-toxic. In the
present study we compared the adjuvant effects between calcium
phosphate nanoparticle (CaP) and alum for their respective immune
enhancement potentials. In a representative study, mice were
immunized with Epstein-Barr virus antigen (EBV), with and without
CaP or alum. Results indicated an increased titer of total IgG antibody
levels in mice injected with CaP encapsulated EBV. Peak responses
occurred between weeks 6 through 14 after primary immunization. In
another study, the influenza virus antigen (flu) was combined with CaP
or alum. Although there was no significant difference in IgG antibody
titer between these two-adjuvant groups, the antigen concentration used
in CaP formulation was 100-fold less than that combined with alum.
These particular results suggest the higher potency of CaP. In yet
another study, the HIV antigen was formulated with CaP or alum to
compare the relative immunogenity. Here again, antibody levels were
similar for both adjuvants. However, the antigen concentration in CaP
based HIV formulation was 50 times less than alum, thus once again
confirming the better potency of the CaP over alum. The combined
results of these studies suggest the advantage, or at least the
bioequivalence of CaP relative to alum. We conclude that CaP is a better
alternative to replace alum in developing vaccines for human use.
57
Sixth Annual Conference
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P5
Adjuvanticity and Other Immunomodulatory Effects Associated
with Lactobacillus reuteri Colonization of the Gastrointestinal
Tract.
W. J. Dobrogosz1, E. Connolly2
1Department of Microbiology, North Carolina State University, Raleigh, NC,
2BioGaia AB, Stockholm, SWEDEN.
Oral administrations of viable, host-specific strains of L. reuteri
protect humans and animals from an assortment of microbial and
chemical challenges. In vitro and in vivo cytokine analyses of gut tissues
have shown this probiotic species to immunomodulate gut mucosal
responses through a variety of pro- and anti-inflammatory inductions.
Additional analyses showed that L. reuteri also has adjuvant activity in
enhancing the IgG antibody response to certain antigens. Casas et al.
(Lactic Acid Bacteria: p. 475. Salminen S and von Wright A, eds, Marcel
Dekker, Inc. NY, 1998) showed that Salmonella typhimurium infected
poults treated with L. reuteri developed higher titers of anti-salmonella
antibodies compared with non-treated controls. Subsequently, Maassen
et al (Vaccine, 18: 2613, 2000) used BALB/c mice to analyze different
Lactobacillus strains with respect to mucosal induction of pro-and antiinflammatory cytokines and the systemic antibody response to
parenterally administered antigens: TNP (trinitrophenyl hapten) and
TNP-CGG (haptenated chicken gamma globulin). They showed that L.
reuteri significantly enhanced the specific IgG antibody response to both
antigens. More recently, human mucosal biopsies showed a significant
increase in CD4 cells in the ileum after the intake of L. reuteri, in
agreement with earlier findings that showed a similar increased
CD4:CD8 ratio in the ileum of chicks after administration of L. reuteri.
Conclusion: Observations derived from human biopsies and animal
model studies indicate that probiotic administrations of L. reuteri have
beneficial immunomodulatory effects on the host’s gut tissues and an
adjuvant effect on certain antibody responses.
P7
Strong CpG Independent Immunostimulation in Humans
and Other Primates by Synthetic Oligodeoxynucleotides with
PyNTTTTGT Motifs.
A. D. Montaner, Sr.
Instituto de Investigaciones Biomédicas, Fundación Pablo Cassará., Buenods
Aires, ARGENTINA.
We have found that in primates, synthetic oligodeoxynucleotides
(ODNs) containing PyNTTTTGT motifs are very effective for
stimulation of B and plasmacytoid dendritic cells (PDC). Several
properties of these ODNs are now presented. Immunostimulatory
activity of ODNs as measured by cell proliferation, flow cytometry, IL6 secretion and IgM secretion assays, either from peripheral
mononuclear blood cells or purified B lymphocytes and PDC. All
performed assays indicated positive immunostimulation by
PyNTTTTGT ODNs and those performed on purified cells indicated
that immunostimulation was direct. The use of a nuclease resistant
phosphorothioate back-bone was not a necessary condition since
phosphodiester PyNTTTTGT ODNs were active. It was also
demonstrated that ODN 2006, a widely used immunostimulant of
human B cells, possess two kinds of immunostimulatory motifs. One of
them mainly composed of two successive TCG trinucleotides located at
the 5´ end and another one (duplicated) of the PyNTTTTGT kind
here described. PyNTTTTGT ODNs are only very active on primate
cells. However, some of them bearing the CATTTTGT motif, have a
small effect on cells from other mammals. Significant differences in the
frequency of PyNTTTTGT sequences between bacterial and human
DNA were not found. Thus, the possibility that PyNTTTTGT ODNs
represent a class of “pathogen associated molecular pattern” is unlikely.
They could, more reasonably, be included within the category of
“danger signals of cell injury”.
58
P6
A Novel Group of Very Potent Non-CpG Immunostimulatory
Oligonucleotides
A.D. Montaner
Instituto de Investigaciones Biomédicas, Fundación Pablo Cassará., Buenos
Aires, ARGENTINA.
It is well known that synthetic oligodeoxynucleotides (ODNs)
containing unmethylated CpG dinucleotides within a given context
stimulate B cells of the vertebrate immune system. We now report that B
cell stimulation in humans could also be very efficiently achieved using
certain kinds of non-CpG ODNs. Immunostimulation activity of
synthetic ODNs were measured by cell proliferation assays, IL6
secretion and IgM secretion from peripheral mononuclear blood cells.
The analysis of hundreds of ODNs led us to the conclusion that there
exist a novel motif for optimal CpG independent immune-stimulation
with general formula PyNTTTTGT wherein Py is C or T and N is
A,T,C or G. Requirements for optimal activity of a given ODN are: a) a
PyNTTTTGT motif located near the central portion of the ODN, b)
20 or more nucleotides long and, c) C or G in position -1 and A or T in
position +1 respect to the motif. In a phosphodiester backbone a
canonical PyNTTTTGT motif is strongly required while in a
phosphorothioate backbone specificity, within certain limits, it is
relaxed.
P8
In Vitro CMI: A Rapid Assay to Determine Antigen-specific T cell
Function in Response to Vaccination
J. B. Woodcock, R. J. Kowalski, J. A. Britz
Cylex Incorporated, Columbia, MD.
Infection with pathogenic organisms results in immune responses to
a broad spectrum of epitopes presented to T-cells by antigen-presenting
cells. Vaccination is effective prophylactically against many infectious
diseases. Many currently used vaccines elicit antibody responses that
provide effective protection. However, antibodies are not effective
against all microorganisms (i.e. tuberculosis, malaria, hepatitis C or
HIV), and T cell-dependent responses may be required to prevent
disease. Cylex has developed an in vitro assay that measures antigenspecific responses of CD3+ lymphocytes that has application to the
assessment of vaccine efficacy. The Cylex in vitro CMI assay employs
proprietary co-stimulation factors and magnetic selection of CD3+ cells
from whole blood to measure immune cell function less than 24 hours
after in vitro exposure to antigens. After incubating a whole blood
sample with the antigen, CD3+ cells are selected, washed and lysed to
release intracellular ATP, which is quantified using a calibration curve.
Increases in intracellular ATP of the CD3+ cells correlate with T-cell
activation and provide a standardized measure of immune cell function.
For this study, the immune response of individuals to foreign antigens
including CMV, Candida albicans, and tetanus was determined.
Volunteers with known natural exposure or vaccination showed
significant responses; whereas, those not exposed or unvaccinated
showed no response. Unlike traditional methods, this technology allows
rapid assessment of cell-mediated immunity to antigenic challenges and
thus the functional activity of T-cells.
on Vaccine Research
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P9
Immunological Assays to Monitor Immune Responses to the
Tumor Antigen CYP1B1.
M. I. Matijevic, J. Sathiyaseelan, R. G. Urban
Clinical Assays, ZYCOS Inc., Lexington, MA.
CYP1B1 is a member of the cytochrome family of proteins recently
shown to be over-expressed in numerous tumor tissues. Naturally
processed peptides have been identified and used to validate the
potential immunogenicity of the CYP1B1 antigen. These findings have
collectively encouraged the development of clinical formulations to
expand CYP1B1, tumor specific, T cell responses in cancer patients.
To support these clinical trials, assay methods were developed to
evaluate general immune status and T cell responses to the CYP1B1
antigens. Assays were first established on samples obtained from
normal blood donors. Test antigens included a mitogen (PHA), a pool
of pathogen derived recall antigens (CEF), and a pool of peptides
spanning the CYP1B1 protein. Each assay utilized a gamma-interferon
ELISPOT assay performed at 24 hours after antigen stimulation of
whole PBMC. The responses (spot forming units/106 PBMC)
observed in thirteen normal donors (mean ± stdev) to PHA and
CYP1B1 were 1801±1644.3 and 22±19.5 respectively. Responses
observed to the CEF pool in seven normal donors were 165±112.5.
Samples from seventeen cancer patients obtained at entry into a
clinical trial were also assayed under identical conditions. The
responses observed in these patients (mean ± stdev) to PHA, CYP1B1
and CEF were 755±1017.7, 94±101.2 and 376±328.8 respectively.
These data support the general immune competence of the study
population and indicate that the assay is an appropriate tool for
immunological analysis. The ability of CYP1B1 specific formulations
to expand T-cell responses in cancer patients is critical.
P11
Liposomal P6 Vaccination Induces Passive Protection Against Non
typeable Haemophilus influenzae (NTHi) in Weanling Rats
A. Rosenthal1, W. A. Ernst2, J. P. Adler-Moore1
1California State Polytechnic University, Pomona, CA,
2Molecular Express, Inc., Los Angeles, CA.
We have previously reported that a liposomal P6 vaccine (L-P6HD) stimulates protection against NTHi meningitis in rats. The
present study was conducted to determine if serum from L-P6-HD
immunized neonatal rats could passively protect naïve rats from NTHi
infection. Seven-day old rats were immunized IP (d0) and SQ (d14)
with L-P6-HD, heat-inactivated NTHi, sham liposomes, or buffer.
Serum was collected (d21), pooled, and rats were given 0.3ml serum
–24h and –12h prior to IP challenge with 2x106 NTHi. Twenty-four
hours after challenge animals were sacrificed, blood collected, plated
and CFU/ml determined. Serum cross-reactivity with different strains
of NTHi was tested in an immunofluorescent antibody/bacterial assay.
Reactivity of serum for P6 protein was evaluated by Western Blot
analysis. Serum from animals vaccinated with sham liposomes, heatinactivated NTHi or buffer, did not reduce bacterial levels in the blood
of naïve animals with 104, 106, 107 CFU/ml respectively. Serum from
L-P6-HD vaccinated rats produced a marked reduction in bacteria (0102 CFU/ml). Serum from L-P6-HD vaccinated rats reacted with four
NTHi strains; NTHi did not react with serum from other vaccine
groups. Western Blot analysis indicated that serum antibodies from LP6-HD vaccinated rats reacted with P6-HD protein and not with other
HD proteins. The results demonstrated that L-P6-HD is a viable
vaccine candidate since serum produced by vaccination of neonatal rats
with L-P6-HD markedly reduced infection when transferred to naive
rats challenged with NTHi and this serum bound with bacteria from
various NTHi strains.
P10
Phase I Study of Meningococcal Outer Membrane
Protein-detoxified Lipooligosaccharide Vaccine in Liposomes
J. Babcock1, J. Berman2, B. L. Brandt3, E. E. Moran3, N. M. Wassef4,
C. R. Alving4, W. D. Zollinger3;
1Clinical Trials, Walter Reed Army Institute Research (WRAIR), Silver Spring,
MD, 2Departmeny of Biology, WRAIR, Silver Spring, MD, 3Department of
Bacterial Diseases, WRAIR, Silver Spring, MD, 4Departmeny of Membrane
Biochemistry, WRAIR, Silver Spring, MD.
We report a phase I clinical study of a meningococcal group B
vaccine consisting of noncovalent complexes of purified outer
membrane proteins (OMPs) and detoxified lipooligosaccharide (dLOS)
in three formulations: 1) adsorbed to aluminum hydroxide; 2)
incorporated in liposomes; and 3) combined in proteoliposomes. Ten
volunteers received each formulation. Two 50µg doses were given six
weeks apart. Volunteers were evaluated for reactogenicity at 30 min and
at 1, 2, and 14 days after each vaccination. Sera were analyzed for
bactericidal antibodies against 4 strains differing in LOS or OMP type.
Serum antibody levels by quantitative ELISA were determined using
native outer membrane vesicles, purified OMPs, and purified LOS as
antigens. The vaccines were well tolerated. Bactericidal assays against a
homologous strain showed a 4-fold or greater increase in titer in six of
seven volunteers in group 1, nine of 10 volunteers in group 2, and five
of 10 volunteers in group 3. GM reciprocal bactericidal titers against a
homologous strain increased from 6.5 to 23.4 in group 1; from 3.5 to
68.6 in group 2; and from 2.8 to 8.6 in group 3. ELISA showed
increases in IgG antibody against both OMPs and LOS.The liposomal
formulation did not enhance antibody responses to the OMPs, but
appeared to be particularly effective in presenting the LOS as an
antigen.
P12
Shigella Invaplex Enhances Cellular and Humoral Immune
Responses to Campylobacter FlaA Protein: Potential for Enteric
Combination Vaccine
R. W. Kaminski1, L. F. Lee2, K. R. Turbyfill1, D. Scott2, P. Guerry2,
E. V. Oaks1
1Walter Reed Army Institute of Research, Silver Spring, MD,
2Naval Medical Research Center, Silver Spring, MD.
An effective Shigella/Campylobacter combination vaccine would make a
significant impact on diarrheal disease caused by two bacterial pathogens
that are continually becoming increasingly resistant to antibiotics.
Recently, a promising Shigella vaccine (Invaplex) consisting of Ipa proteins
and LPS was shown to enhance the immune response to ETEC
colonization factor antigens. In the present study the immunogenicity of
the Shigella Invaplex and the Campylobacter FlaA protein was evaluated in
mice for potential use as a combination vaccine. Mice were immunized
intranasally (0, 2, 4 weeks) with FlaA protein (1 ug) formulated with and
without Invaplex or recombinant mutant E. coli labile toxin (LT). Serum
was assayed for anti-FlaA IgG and IgA using ELISA. Proliferative
responses in spleen and cervical lymph nodes (CLN) were assessed using
FlaA and Invaplex antigens. After three immunizations, Invaplex
formulations increased the anti-FlaA serum IgG 8 to16-fold and IgA 4 to
8 fold compared to FlaA alone with comparable titers to FlaA-LT.
Invaplex stimulated a more rapid anti-FlaA immune response exemplified
by serum IgG and IgA responses after two immunizations whereas mice
immunized twice with FlaA (1 ug) alone had undetectable antibody levels.
Shigella and Campylobacter-specific proliferative responses were detected
in splenic and CLN cells from animals immunized with FlaA-Invaplex or
FlaA-LT. These results indicate Invaplex is a potent mucosal adjuvant
capable of enhancing cellular and humoral immunity. The addition of
Shigella Invaplex and Campylobacter antigens shows promise for future
enteric combination vaccines.
59
Sixth Annual Conference
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P13
Activax®: Towards the Development of a Multivalent Oral
Vaccine for Travelers’ Diarrhea
G. S. Nabors, P.. Hinds, II, R. Kango
Antex Biologics, Gaithersburg, MD.
Presently there is no vaccine licensed in the U.S. to protect against
the major bacterial causes of travelers’ diarrhea. Such a vaccine would
be beneficial for both civilian and military personnel traveling abroad.
Antex’s strategy has been to develop an oral vaccine composed of
formalin-inactivated Shigella spp. and Campylobacter jejuni cells, grown
using Nutriment Signal Technology to enhance expression of virulence
factors and phenotypes, with a mutant detoxified E. coli heat labile
toxin LT(R192G) as adjuvant. Using the guinea pig ocular Shigella
challenge model, it was found that animals immunized with trivalent S.
sonnei+C. jejuni+mLT(R192G) vaccine were as resistant to a
heterologous S. sonnei strain as those immunized with S. sonnei cells
alone. To begin development of a dry formulation of killed whole cells,
a monovalent inactivated C. jejuni vaccine was lyophilized. Mice
immunized once i.p. with liquid (never lyophilized) or
lyophilized/reconstituted vaccine produced antibodies to C. jejuni
whole cells. Flagellin is a known protective antigen for C. jejuni, and
anti-flagellin responses following immunization with lyophilized
vaccine were superior to those found following immunization with
liquid vaccine. A soluble fraction of the lyophilized vaccine contained
less flagellin than that prepared from the liquid vaccine, indicating that
lyophilization allowed for more flagellin to remain in a cell-associated,
potentially more immunogenic form. We conclude that a trivalent
vaccine composed of inactivated whole cells and adjuvanted with
LT(R192G) is a viable vaccine candidate for Travelers’ Diarrhea, and
the creation of a dry formulation of this vaccine may be achievable.
P15
Developing an Immunogenic Consensus Sequence T cell Epitopes
for the GAIA Cross-Clade HIV Vaccine
A.S. De Groot1, H. Sbai2, E. A. Bishop2, S. Foti2, J. Franco2, M. Lally3,
D. B. Weiner4, K. H. Mayer3, C. C. J. Carpenter3, W. Martin5
1Department of Community Health, Brown University, EpiVax, Inc,
Providence, RI, 2Community Health, Brown University, Providence, RI,
3Immunology Center, Miriam Hospital, Providence, RI, 4University of
Pennsylvania School of Medicine, Philadelphia, PA, 5EpiVax, Inc,
Providence, RI.
Broad cellular immune responses to HIV-1 T cell epitopes are
linked to protection from the progression to AIDS. Two computer
algorithms (Conservatrix and EpiMatrix) were used to select for highly
conserved peptides from HIV-1 isolates obtained from public HIV
sequence databases. Criteria for inclusion in our study included (1)
conservation among HIV-1 isolates; (2) potential binding to class I and
II HLA molecules; and (3) promiscuity. Recognition of these HIV-1 T
helper and HLA A2-restricted peptides was evaluated by IFN-g ELIspot
assays using peripheral blood monocytes (PBMCs) from more than 50
HIV infected individuals, of which 25 were long term non-progressors.
The remaining subjects had CD4 >250 and a viral load < 5,000
copies/ml. 90% of the class II-restricted peptides derived from env
protein were confirmed to be immunogenic as evaluated in ELIspot
assays. These epitopes did not induce IFN-g secretion from PBMCs of
HIV-seronegative control subjects. 80% of HLA A2-restricted peptides
were confirmed to be immunogenic. These epitopes were derived from
all nine HIV proteins. Epitopes derived from gag and pol were the most
broadly recognized. These data confirm the utility of bioinformatics
tools to identify immunogenic T cell epitopes for a globally relevant
HIV vaccine.
60
P14
Lactococcal Ghosts as Carrier in S. pneumoniae Mucosal
Subunit Vaccines
K. Leenhouts1, P. Adrian2, M. van Roosmalen1, R. Kanninga1, S. Estafao2,
A. Steen3, G. Buist3, J. Kok3, O. Kuipers3, R. de Groot2, G. Robillard1,
P. Hermans2
1BioMaDe Technology Foundation, Groningen, NETHERLANDS, 2Department of
Pediatric Infectious Diseases, Erasmus University Rotterdam, Rotterdam,
NETHERLANDS, 3Department of Molecular Genetics, State University
Groningen, Groningen, NETHERLANDS.
Streptococcus pneumoniae is the leading etiological agent of severe
infections such as septicemia, meningitis, pneumonia, and otitis media.
In our ongoing studies on the molecular epidemiology and pathogenesis
of S. pneumoniae, we have identified pneumococcal proteins with
vaccine potential. One of these proteins, PpmA, has been shown to elicit
immune protective potential in our mouse pneumonia model.
The non-genetically modified lactococcal ghosts have been shown to be
an efficient carrier in oral immunizations of rabbits and mice to elicit
strong anti-malaria immune responses. Here we describe the
construction of lactococcal ghosts that display on their surface the S.
pneumoniae PpmA fused to the lactococcal AcmA cell-wall binding
domain and we investigated in a pilot experiment the ability of these
ghosts to protect mice after nasal and oral immunizations from a lethal
nasal S. pneumoniae challenge.
P16
Induction of High Levels of HIV-Gag Expression and Anti-Gag
Immune Response Elicited by Lysosomal-associated Membrane
Protein (LAMP) Luminal Domain in LAMP/Gag DNA vaccine
chimeras
L. B. Arruda, P. R. Chikhlikar, M. Maciel Jr., J. Thomas August, E. T. A.
Marques Jr.
Department of Pharmacology, Johns Hopkins University School of Medicine,
Baltimore, MD.
DNA vaccine chimeras encoding antigens with the lysosomeassociated membrane protein (LAMP) cytoplasmic domain containing the
C-terminal YXXO lysosomal targeting signal elicit localization of the
chimeric protein to MHCII compartment and an enhanced B- and T-cell
immune responses. We applied this LAMP targeting system to HIV-1
Gag, which has been described as a critical component of HIV vaccines.
In these studies we found that trafficking of the LAMP/Gag chimera
requires the presence of the luminal domain of LAMP as well as the
cytoplasmic sequence. Moreover, addition of the N-terminal luminal
sequence upstream to Gag promotes increased expression of native Gag,
independent of the viral protein Rev. Serial 3’ to 5’-deletions of the
LAMP luminal domain demonstrated that Gag expression increased
according to the length of the luminal sequence and reached the
maximum level with the unmodified LAMP luminal domain in the
correct orientation. Additionally, the intact luminal domain promoted
maximal trafficking of the LAMP/Gag chimera to the MHC II
compartment and the greatest levels of B and T cell immune responses.
These data indicate that the combination of high gag expression and
cellular trafficking promoted by the LAMP luminal domain in a
LAMP/Gag chimera is our most effective HIV-1 Gag DNA vaccine
construct. Furthermore, these results also suggest that LAMP luminal
domain may play a role with other LAMP/antigen chimeras. Financial
Support: NIH, CAPES
on Vaccine Research
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P17
Cell-based ELISA for Potency Measurement of FluMist™ –
a Live, Attenuated Influenza Virus Vaccine
K. Sra, J. Xu, J. Reddy, K. Schweighofer, J. Soni, J. Pham, A. Lewis,
A. Pan, H. Mehta
Analytical Biochemistry, MedImmune Vaccines, Mountain View, CA.
P18
Comparability of a Manual and Semi-Automated Median Tissue
Culture Infective Dose (TCID50) Assay for the Potency
Measurement of FluMist™ – A Live, Attenuated Influenza
Virus Vaccine
A. Pan, J. Reddy, J. Xu, J. Soni, J. Pham, A. Lewis, K. Sra, W. White, I. Cho,
E. Gopinath, H. Mehta
Analytical Biochemistry, MedImmune Vaccines, Inc., Mountain View, CA.
Background: Median tissue culture infective dose (TCID50) assay
is widely used for the potency measurement of live virus and live virus
vaccines. We describe a cell-based ELISA (CELISA) as a simpler and
faster alternative to the traditional, long and labor intensive TCID50
assay to measure potency of influenza virus in FluMistTM. Briefly,
confluent monolayers of Madin-Darby Canine Kidney (MDCK) cells
in 96-well microtiter plates are infected with sample containing live
influenza virus, fixed with formalin 16-18 hours post-infection and
reacted with influenza virus-specific monoclonal antibody (MAb).
Virus antigen-bound MAb is then detected using anti-mouse
IgG~Peroxidase and substrate to develop soluble colored product, the
optical density (OD) of which is measured spectrophotometrically.
The potency of live influenza virus is calculated from a standard curve
generated using live influenza virus calibrators with known
log10TCID50 values obtained with a validated TCID50 potency
assay. CELISA is shown to be linear (r2 > 0.95) in the range 4.9 – 6.7
log10TCID50. Between-day, between-analyst, between-plate, within
plate (residual) and total variability (standard deviation in
log10TCID50) were <0.21, <0.05, <0.11, <0.06, and <0.22,
respectively. The potency of several vaccine and wild-type influenza
A/H1N1, A/H3N2 and B strains measured by CELISA are
comparable (+ 0.3 log10TCID50) to the potency measured in parallel
by the validated TCID50 potency assay. CELISA is capable of
measuring potency of up to 10 samples/plate in 2 days in contrast to 2
samples/plate in 6 days for the validated TCID50 potency assay.
The validated TCID50 potency assay is currently used for the
potency measurement of influenza virus in FluMistTM. A SemiAutomated TCID50 potency assay is described in which two laborintensive steps of the validated manual potency assay are improved.
These are (i) use of an automated pipetting station for serial sampledilutions and infection of MDCK monolayers in place of manual
dilution steps, and (ii) use 6-days post-infection of a 96-well plate reader
to measure spectrophotometrically the product of MTT (a vital dye (3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) widely
used as an indicator of cell health/viability) for the assessment of
influenza virus induced cytopathic effect (CPE) in MDCK monolayer in
place of manual observation of each well using a light microscope. The
semi-automated TCID50 potency assay was developed and validated to
demonstrate precision (values in log10TCID50; repeatability: <0.25;
intermediate precision: SD(Day) <0.3; SD(Analyst) and
SD(Instrument) <0.4; and reproducibility: at the 90% confidence
interval within + 0.3), linearity, accuracy and range (slope 1 + 0.1). The
Semi-Automated TCID50 potency assay was shown to provide
equivalent mean log TCID50 values to the validated manual TCID50
potency assay (at the 90% confidence interval + 0.3 log10TCID50). In
conclusion, results provide support for the use of a pipetting station and
MTT dye to measure the potency of influenza virus in FluMistTM.
These improvements also increase the testing throughput.
P19
P20
Correlation Between Influenza Vaccine Induced Cytokine
Production and Change in CYP3A4 Activity.
M. S. Hayney1, R. M. Fohl1, D. Muller2;
1School of Pharmacy, University of Wisconsin, Madison, WI,
2Medical School, University of Wisconsin, Madison, WI.
A number of clinical reports of drug interactions with influenza
vaccine have been made. Many of the reports involved drugs
metabolized by CYP3A4. We hypothesized that changes in CYP3A4
activity following influenza immunization would correlate with
cytokine production or age. Twenty-four healthy subjects were
recruited for this study and enrolled prior to the beginning of the
influenza season. Each subject had an erythromycin breath test
(ERMBT) and blood draw for lymphocyte culture prior to and on day
7 following influenza immunization. Hemagglutination inhibition
assays (HIA) were done prior to immunization and on day 28.
Cytokine production by lymphocytes cultured with influenza antigen
was measured by ELISA. Eight men and sixteen women participated
in the study. The age range was 20 to 66 years (mean 38.7 years; SE
2.9). Interferon g (IFNg) production significantly inversely correlated
with change in ERMBT (correlation coefficient -0.614; p<0.02)
although the overall change in ERMBT was not statistically significant
(mean –4%; p=0.28). No correlations were found with interleukin-10
production, age or antibody concentrations. The IFNg production
correlates with change in ERMBT. This correlation supports in vitro
findings of decreased CYP3A4 expression and activity with IFNg
exposure.
Epidermal Powder Immunization against Influenza
D. Chen, Q. Chu
PowderJect Vaccines, Madison, WI.
Influenza viruses cause severe respiratory tract infections in millions
of people every year and a high mortality rate in the elderly and highrisk populations. The current influenza vaccine, consisting of three split
influenza viruses updated every year, has a variable efficacy when
administered by intramuscular (IM) injection using a syringe and
needle, depending on the recipient’s age and health status. The efficacy
in the elderly population is particularly low. There is a great need for an
influenza vaccine product with improved efficacy. Our studies
demonstrated that epidermal powder immunization (EPI) of mice with
influenza vaccine elicited augmented serum antibody responses, mucosal
antibody responses, and even cell-mediated immunity to a subunit
influenza vaccine. Using QS-21, EPI induced significantly higher serum
HI titers in non-human primates than traditional needle injection with
influenza vaccine. A phase I clinical study involving 36 volunteers
demonstrates that EPI with influenza vaccine generates a robust
immune response in humans and the immune response is at least as
strong as that achieved by the same dose of vaccine administered by
needle injection. The important advantages of EPI over traditional
needle injection include delivery of antigens directly to the Langerhans
cells in the skin and active participation of both the innate and the
adaptive arms of the immune system in the immune responses.
61
Sixth Annual Conference
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P21
Evaluation of Immunity to Mumps Virus: Comparison of Plaque
Reduction Neutralization Assay (PRN) to ELISA
J. P. Mauldin1, K. Carbone1, R. Yolken2, S. Rubin1;
1Center for Biologics Evaluation and Research, FDA, Bethesda, MD,
2Department of Pediatrics, The Johns Hopkins University, Baltimore, MD.
Currently either plaque reduction neutralization assay (PRN) or
hemaglutination inhibition assay (HIA) are acceptable measures of
protective serological immune responses to mumps. However, there is
debate as to whether rapid and quantitative serological assays (e.g.,
ELISA) can be used as indicators of mumps serological responses. Thus,
we compared serological responses to wild type mumps in a group of 75
human sera using two commercially available mumps IgG ELISAs
(Wampole Laboratories, Cranbury, New Jersey, USA, and IBL,
Hamburg, Germany), to those obtained using an in-house plaque
reduction neutralization (PRN) assay. Because the induction of a
neutralizing antibody response is a reasonable index of immunity against
mumps virus, results of the PRN assay were used as the standard against
which ELISA results were compared. The results indicate that the
specificity of the two ELISAs ranged from 83%-91% and the sensitivity
ranged from 72%-76%. These results suggest that assays that detect
functional antibody, e.g., virus neutralization assays, are of greater utility
than ELISAs for assessing mumps immunity.
P23
Development of a Mucosal Vaccine Against RSV
S. Singh, S. Pillai, K. Scissum-Gunn
Department of Biology, Alabama State University, Montgomery, AL.
The antigenic regions of respiratory syncytial virus (RSV) F gene
corresponding to nucleotides 1248-1583 were PCR amplified and
cloned into a vector containing modified cholera toxin gene (ctxA2B).
The recombinant plasmids were used to transform E. coli BL21 (DE3)
cells and the protein was expressed. The fusion protein (FA2) was
expressed and analyzed on SDS gels. Recombinant protein was mixed
with acid denatured CTB to form a holotoxin like chimera, designated
as FA2-CTB. The proper folding and reassociation of FA2-CTB
chimeric protein was confirmed by GM1-ELISA. The presence of the
RSV F protein and CTB in the chimera was also confirmed by
immunoblotting using anti-RSV and anti-CT polyclonal antibodies,
respectively. The purified FA2-CTB chimeric protein is under study to
evaluate the effectiveness in mice against RSV infection.
62
P22
Vaxfectin Enhances Antibody and Cd8+ T Cell Responses to Low
Doses of Plasmid Encoding a Malaria Antigen
M. Sedegah;
Malaria Program, Naval Medical Research Center, Silver Spring, MD.
We have evaluated the capacity of the cationic lipid based
formulation, Vaxfectin, to enhance the immunogenicity and protective
efficacy of plasmid DNA encoding P. yoelii circumsporozoite protein
(PyCSP). PyCSP DNA was formulated with PBS or Vaxfectin at a 4:1
pDNA:Vaxfectin molar ratio. BALB/c mice were immunized
intramuscularly with 2 mg, 10 mg or 50 mg of PyCSP DNA in PBS or
Vaxfectin. In homologous DNA immunization regimens, mice were
immunized four times at four week intervals with PyCSP DNA in PBS
or Vaxfectin. In heterologous DNA prime/virus boost regimens, mice
were primed three times at four week intervals with PyCSP DNA in PBS
or Vaxfectin, and boosted with PyCSP recombinant poxvirus 4 weeks
later. Immunogenicity (indirect fluorescent antibody test and ELIspot
interferon-gamma responses) and protective efficacy following P. yoelii
sporozoite challenge were assessed. In both homologous and
heterologous regimens, formulation of pDNA with Vaxfectin
significantly increased antibody and IFN-g responses and enhanced
protection, as compared with PBS, at 2 mg and10 mg but not 50 mg
doses. The immune enhancement effect of Vaxfectin was most
pronounced at the lowest dose of DNA tested. Data demonstrate that
formulation of pDNA with a cationic lipid-based formulation such as
Vaxfectin can enhance antibody and cellular immune responses as well
as protective efficacy at low doses of pDNA. This may have important
implications for the clinic, if the poor immunogenicity of DNA vaccines
in human studies to date is related to the dose of DNA/kg body weight.
P24
C3d as a Genetic Adjuvant for DNA Vaccines Diverts the Immune
Response Against Malaria
E. S. Bergmann-Leitner1, S. Scheiblhofer2, R. Weiss2, D. Winter3,
E. H. Duncan1, E. Angov1, F. Khan1, G. Tsokos3, J. Thalhamer2, J. A. Lyon1;
1Department of Immunology, Walter Reed Army Institute of Research, Silver
Spring, MD, 2Institute for Biochemistry, University of Salzburg, Salzburg,
AUSTRIA, 3Department of Cellular Injury, Walter Reed Army Institute of
Research, Silver Spring, MD.
The circumsporozoite protein (CSP) of Plasmodium spp. parasites is
the most extensively studied of the malaria vaccine candidates. Genetic
vaccination of mice with a naked DNA plasmid encoding the P. berghei
CS protein gene induces a strong protective effect against sporozoite
challenge. Gene gun vaccination induces complete protection against
Plasmodium berghei malaria challenge in BALB/J and C57BL/6 mice,
however, at least two immunizations at 4-week intervals are needed to
induce this level of protection. Protection correlates with induction Th2
type immunity and of antibodies that are specific for the C-terminal
flanking sequence. We sought to improve the efficacy of this vaccine by
constructing a chimera (CSP/2C3d) consisting of the CS protein gene
and two copies of the C3d fragment of the murine C3 complement
protein. This approach was shown to enhance the efficacy of anti-viral
DNA vaccines. Compared to vaccination with CS protein gene,
vaccination with CSP/2C3d chimeric gene abrogated protection against
malaria, had no effect on the number of IFN-g producing cells,
suppressed IL-4 producing T lymphocytes, and suppressed induction of
CS protein-specific antibody, including a strong suppression of antibody
to the C-terminal flanking region. This study indicates that the use of
C3d as a genetic adjuvant is not a universal approach for improving
genetic vaccines.
on Vaccine Research
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P25
Poxvirus Vaccines - the Myxoma Virus and European Rabbit Model
M. M. Adams, B. H. van Leeuwen, P. J. Kerr
Pest Animal Control Cooperative Research Centre, CSIRO Sustainable
Ecosystems, Canberra ACT, AUSTRALIA.
P26
Bovine Pulmonary Vascular Disturbances Following Exposure to
Vaccine Derived Mannheimia (Pasteurella) haemolytica Antigens
B. Weekley, P. Eyre, H. Veit, N. Sriranganathan;
College of Veterinary Medicine, Virginia Polytechnic Institute, Blacksburg, VA.
Myxoma virus is a leporipoxvirus and the causative agent of the
lethal disease myxomatosis in European rabbits. The vaccines available,
live attenuated myxoma virus and rabbit fibroma virus, are not
permitted in Australia due to fears the live virus could ‘escape’ and
vaccinate wild rabbit populations where myxoma virus is an important
biological control. Inactivated vaccines are not protective for myxoma
virus or other poxviruses. The goal of this project is to investigate novel,
non-transmissible myxoma virus vaccines including DNA vaccines and
deletion mutant viruses. The ability of four myxoma virus antigens
(M055R, M073R, M115L, M121R) to protect domestic rabbits from
challenge with virulent myxoma virus, when delivered as an
intramuscular DNA vaccine in conjunction with rabbit interleukin-2 or
interleukin-4, was tested. Immunized rabbits were not protected from
challenge, although both cell-mediated and humoral immune responses
were induced. Live myxoma virus vaccines have been constructed by the
deletion of three important immunomodulatory genes: the gammainterferon binding protein MT-7, myxoma growth factor M10L and an
anti-apoptotic factor M11L, from an attenuated field strain of the virus.
Although able to completely protect rabbits from subsequent challenge,
deletion mutants tested so far still cause mild symptoms of
myxomatosis, disseminate to distal sites in the host and may be
transmissible. The challenge of this work is to obtain a balance between
an aggressive, possibly harmful or transmissible vaccine guaranteed to
protect the host upon challenge and a completely innocuous vaccine
that provides only partial protection.
The acute pathophysiologic effects of Mannheimia (Pasteurella)
haemolytica vaccine-derived antigens on the pulmonary circulation was
investigated in calves. Previous studies have revealed that vascular
autonomic function is altered in bovine respiratory disease complex.
This study was undertaken to evaluate vascular pulmonary changes
which may occur in response to vaccine derived bacterial antigens prior
to development of protective immunity. Twelve Jersey bull calves were
immunized with saline, live Mannheimia haemolytica (109 organisms
per animal, intramuscular) or Mannheimia haemolytica leukotoxoid
obtained from a commercial vaccine. Three days after antigen
exposure, the ex vivo response if intrapulmonary artery and vein to the
autonomic agonists carbachol, methoxamine and isoproterenol were
assessed. Dose-response studies with the autonomic agonists reveal
that endothelial-dependent cholinergic arterial vasodilation is reduced
and venoconstriction is potentiated in antigen exposed animals
(p<0.05). Pretreatment with the endothelial nitric oxide synthetase
inhibitor N G-monomethyl-L-arginine (L-NMMA) potentiates the
vasoconstriction in Mannheimia haemolytica exposed animals. Animals
exposed to vaccine-derived antigens have an enhanced vasorelaxant
response to isoproterenol and an impaired vasoconstrictor response to
methoxamine. These data suggest that vaccination induced alterations
in pulmonary haemodynamics prior to development of protective
immunity may increase susceptibility to stress-induced disease.
P27
P28
Failure of Antibiotic Treatment in Horses and Effect of Autogenous
Vaccines.
O. J. Nolte1, H. E. Weiss2
1Department of Hygiene and Medical Microbiology, Hygiene-Institut,
Heidelberg, GERMANY, 2CVUA, Heidelberg, GERMANY.
In veterinary practice autovaccines are frequently used in cases were
standard therapy fails to control infection. Autovaccines are therapeutic
vaccines (immunomodulators) made from a culture of micro-organisms
found to be responsible for a disease. We have compared the effect of
antibiotic treatment and autovaccination for the treatment of horses on
a retrospective basis. Analyzing data on autovaccination therapy in 175
horses which were treated by 15 veterinarians in Germany between 1999
and 2001. In 2002, questionnaires were sent to the veterinarians to raise
data about previous therapy, duration of the disease, effect of standard
therapy/autovaccination and side effects observed following application
of autovaccines. The majority of horses received previous treatment
with antimicrobial drugs (20.3% of the animals were treated with a
single drug, 41.8% with two or more drugs) None of the animals was
found to be healthy when standard therapy was finished although
41.8% were reported to have responded with little and 11.4% with
distinct improvement. Following autovaccination 34.2% of the animals
showed distinct improvement of their condition and 34.8% were found
to be healthy by the attending veterinarian. Most of the animals showed
at least one side effect following autovaccination. The most frequent side
effect was a swelling at the site of injection. Three horses displayed
severe side effects. In cases of antimicrobial therapy failure, autovaccines
are a good alternative for treatment, at least in veterinary practice. The
advantage of autovaccines: easy manufacturing process and no risk of
development of resistance.
Immune Response in Chickens Following the Oral Administration of
Plant-Expressed Heat Labile Toxin
S. R. Webb1, T. J. Miller2, M. Fanton2, H. S. Mason3, D. D. Kirk4,
C. Artzen4;
1Dow AgroSciences, Indianapolis, IN, 2Benchmark Biolabs Inc, Lincoln, NE,
3Department of Plant Biology, Arizona State University, Tempe, AZ, 4Arizona
State University, Tempe, AZ.
The development of plant-based oral vaccines offers a number of
benefits when compared to existing antigen manufacturing and delivery
technologies including; needle-less delivery, elimination of the cold
chain and improved safety. For an oral vaccine to be effective the antigen
must navigate the complex environment of the digestive tract and
interact with GALT. Development of plant-based oral vaccines requires a
detailed understanding of plant-expressed antigen interaction with
GALT and subsequent serological response. The objective of these
studies was to understand the immune response of native LT following
oral and intranasal administration to poultry. A comparison of the
serological response in poultry between native and plant-expressed LT
was also made. LT is a known immunostimulator and a mucosal surface
immunogen in mammals, however, there is no detailed information on
the use of LT in poultry. There are no reports on the serological response
of chickens to native or attenuated LT in chickens when delivered by the
mucosal route. These studies demonstrate that native LT and LTB
induce a serological response detected in serum IgG by 21 days
following intranasal and oral administration in poultry. Similarly, NT-1
cells expressing native LTB and an attenuated form of LTA induced
similar serological responses in poultry following oral and intra-nasal
delivery. Furthermore, no adverse effects of the plant material or the
plant-expressed toxin were observed in the birds.
63
Sixth Annual Conference
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P29
A Plant-based Mucosal Vaccine For Amebiasis
F. Medina-Bolivar1, V. Funk1, R. Wright1, B. Mann2, S. Stroup2,
W. Petri Jr.2, C. Cramer1;
1Department of Plant Pathology, Virginia Tech, Blacksburg, VA, 2Department
of Medicine, University of Virginia Health System, Charlottesville, VA.
Amebiasis, an infection caused by the parasite Entamoeba
histolytica is responsible for approximately 50 million illnesses and
100,000 deaths per year, making it the third leading cause of death
worldwide due to parasitic diseases in humans. In order to develop
cost-effective systems for mucosal vaccines, we have linked plantbased antigen bioproduction with development of a plant-derived
lectin adjuvant/carrier that enhances mucosal immunity and antigen
purification. In previous work, this mucosal adjuvant/carrier (MAC1)
was shown to be as effective as cholera toxin in eliciting a mucosal
response to GFP [Medina-Bolivar et al., (2003) Vaccine 21, 9971005]. In this research we have genetically fused MAC1 to a potential
protective antigen derived from the galactose/N-acetylgalactosamine
binding lectin of E. histolytica. To optimize expression in plants, the
DNA sequence encoding the antigenic amoebic protein was codonoptimized. The fusion protein was expressed in tobacco plants and
hairy roots and will be purified and used in immunization studies in
mice.
P31
Expression of a Tuberculosis Antigen in Plants
M. Rigano, D. D. Kirk, L. Alvarez, J. Pinkhasov, Y. Jin, A. M. Walmsley;
Department of Plant Biology, Arizona State University, Tempe, AZ.
Transgenic plants are potentially safe and inexpensive vehicles to
produce and mucosally deliver protective antigens. However, the
application of this technology is limited by the poor response of the
immune system to non-particulate, subunit vaccines. Co-delivery of
therapeutic proteins with carrier proteins could increase the
effectiveness of the antigen. This paper reports the ability of transgenic
Arabidopsis thaliana plants to express a fusion protein consisting of a
carrier protein and a 6 kDa tuberculosis antigen, the early secretory
antigen target (ESAT-6). The coding regions of the carrier protein and
ESAT-6 were transcriptionally fused then transformed into Arabidopsis
thaliana using Agrobacterium tumefaciens. The resulting transgenic
plants were characterized through PCR, ELISA, Western and Northern
analysis. Both components of the fusion protein were shown to retain
native antigenicity through GM1-dependent ELISA. Arabidopsis
thaliana was able to express an antigenically active carrier
protien/ESAT-6 fusion protein. Small animal trials in collaboration
with the TB research materials and vaccine testing contract (Colorado
State University) will test the immunogenicity of this fusion protein.
64
P30
Efficacy of an Edible, Plant-derived Immunocontraceptive Vaccine in
Mice and Voles
A. M. Walmsley1, D. D. Kirk1, L. Rowland2, T. J. Miller3, H. S. Mason1;
1Department of Plant Biology, Arizona State University, Tempe, AZ,
2Department of Natural Resources, Cornell University, Ithaca, NY, 3Benchmark
Biolabs, Inc., Lincoln, NE.
An edible immunocontraceptive vaccine would increase the ease of
delivery and cost effectiveness of current immunocontraceptive
technology thereby enabling its use as an alternative method for
reducing populations of problem animal species. In an attempt to orally
deliver an immunocontraceptive vaccine, we generated transgenic
tomato plants (Lycopersicon esculentum cv. TA234) that expressed a
fusion protein consisting of a carrier protein and an
immunocontraceptive epitope. The transgenic tomatoes were fed to
adult, female mice (Mus musculus) and voles (Microtus ochrogaster) and
the number of litters and pups recorded. Female mice that received a
test diet containing transgenic tomatoes displayed decreased fertility
with respect to pups they birthed. Species specificity of the peptide was
shown when mice receiving the test diet of transgenic tomatoes and
adjuvant displayed reduced litter size (45.3%) while no effect was
observed in vole treatments. In this study an orally delivered, plantderived, carrier protein and immunocontraceptive epitope coadministered with a saponin adjuvant displayed species-specificity and
reduced mice fertility by 45.3%. We believe the vaccine described in this
report has potential to act as an effective, edible immunocontraceptive
vaccine.
P32
Childhood Vaccines: Ensuring an Adequate Supply Poses
Continuing Challenges
J. L. Major1, L. Y. A. McIver1, T. Saiki1, L. Spangler1, F. Pasquier1,
J. Heinrich2;
1Health Care, U.S. General Accounting Office, Seattle, WA, 2Health Care,
U.S. General Accounting Office, Washington, DC.
In late 2001, the Centers for Disease Control and Prevention (CDC)
reported shortages in five of the eight recommended childhood vaccines.
This review examines the extent to which the shortages affected
immunization policies and programs across the nation, the factors that
contributed to the shortages, and the strategies federal agencies are
considering to help mitigate disruptions in the vaccine supply. To assess
the effect of shortages on immunization programs, we surveyed 64 state,
territorial, and local immunization programs supported by CDC, and
examined temporary changes in recommended immunization schedules.
To understand the contributing factors to the shortages, we visited the
four primary vaccine manufacturers and determined how federal
regulatory procedures affect vaccine production. To identify strategies
being considered by federal authorities to prevent shortages, we reviewed
studies and recommendations to strengthen the vaccine supply, attended
advisory panel meetings, and interviewed agency officials and other
vaccine experts. Vaccine shortages prompted federal authorities to
recommend deferring some immunizations and caused the majority of
states to reduce immunization requirements. Multiple factors contributed
to the shortages, affecting both supply and demand. While these factors
have largely been resolved, the potential exists for shortages to recur.
Federal agencies are exploring options to help stabilize the nation’s
vaccine supply, but few long-term solutions have emerged. Expanding
CDC vaccine stockpiles is receiving wide consideration as a short-term
strategy, but this will require a substantial planning effort.
on Vaccine Research
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P33
Using the Vaccine Formulary Selection Algorithm for Establishing
Economical Value of New Combination Vaccines
E. A. Medina1, D. A. Allwine1, B. G. Weniger2;
1Austral Engineering and Software, Inc., Athens, OH, 2Immunization Safety
Branch, National Immunization Program, Centers for Disease Control and
Prevention, Atlanta, GA.
P34
Analyzing the Economic Value of Combination Vaccines by Reverse
Engineering a Vaccine Selection Algorithm
S. H. Jacobson1, E. C. Sewell2, T. Karnani1;
1Department of Mechanical and Industrial Engineering, University of Illinois,
Urbana, IL, 2Department of Mathematics and Statistics, Southern Illinois
University Edwardsville, Edwardsville, IL
The vaccine selection algorithm tool assembles best-value
formularies satisfying the U.S. Recommended Childhood
Immunization Schedule. Using operations research, it optimizes the
most economical set of vaccines, recognizing costs of purchase,
preparation, injection, and potentially other factors. The effect of new
vaccines on best-value formularies was studied by varying the purchase
price of a hypothetical DTPa-HIB-IPV vaccine in a pre-filled syringe
which could be administered at months 2, 4, 6, and 15-18. Clinic visits
were set to $40.00, injection costs to $15.00, and preparation time for
pre-filled syringes, liquid in vials, and lyophilized powder to $0.25,
$0.75, and $1.25, respectively. It competed against Average Wholesale
Prices for existing U.S. vaccines. Matching acellular pertussis antigens
by manufacturer was required for all doses. DTPa-HIB-IPV(AVP)
appeared in the best-value formulary with three doses when priced at
$83.51 each, and with four doses at $48.25. DTPa-HIB-IPV(GSK)
won one dose at $84.12, three at $81.03, and 4 at $53.02. Five doses of
DTPa-HIB-IPV from a new manufacturer without existing pertussis
product(s) would be in the lowest-cost formulary at $72.73 each only if
also licensed for age 4-6 years. The study illustrates how the algorithm
can establish the economic value of a new vaccine. It can be used by
manufacturers in order to competitively price new vaccines, and by
purchasers to establish which to buy and how much they ought to pay.
An operations research algorithm was designed to identify
formularies that satisfy the pediatric immunization schedule at the
lowest overall cost. The algorithm has been adapted using reverse
engineering to determine the value of combination vaccines for which
monovalent vaccines exist. The algorithm is used to determine to
identify appropriate public sector prices for a pentavalent pediatric
combination vaccine. Different economic factors were varied to assess
the sensitivity of these factors to the combination vaccine prices. The
price for the combination vaccine was between $1.99 and $19.00 more
than the sum of the prices for the monovalent vaccine components, as
the cost of administering an injection increased from $1.00 to $15.00,
with no perinatal hepatitis B dose administered, and three dose of the
combination vaccine in the vaccine formulary. Similar results were
obtained with the perinatal Hepatitis B dose administered and different
numbers of doses of the combination vaccine. Reverse engineering the
vaccine selection algorithm provides a rational tool for assessing the
appropriate price for certain types of combination vaccines. The results
indicate that combination vaccine price premium are warranted,
dependent upon the price one is willing to pay to avoid additional
injections. As new combination vaccines enter the market, the reverse
engineering tool provides a resource for pediatric vaccine purchasers to
determine if the price premium for such products is warranted for their
particular environment.
P35
P36
Coverage and Determinants of Immunization Uptake Following
Implementation of a Universal Infant Hepatitis B Immunization
Program in British Columbia, Canada
V. P. Remple1, C. McIntyre1, K. Pielak1, R. White1, W. Wu1, M. Bigham2;
1Department of Epidemiology, British Columbia Centre for Disease Control,
Vancouver, BC, CANADA, 2Canadian Blood Services, Vancouver, BC, CANADA.
British Columbia introduced a universal infant hepatitis B
immunization (HBI) program on March 1, 2001, offering HB vaccine
to all infants at age 2, 4, and 6 mo. The purpose of this study was to
evaluate coverage and determinants of HBI. Letters were sent to a
random sample of 968 BC households with infants born Jan-Jun/01
inclusive, followed by a structured telephone interview. In addition to
collecting parental-reported HBI and demographics data, a scale based
on Health Belief Model(HBM) concepts explored relevant determinants
of HBI. HBM concepts were scored on a 1(strongly agree) to 5(strongly
disagree) Likert scale. Statistics included descriptive and stepwise
logistic regression. Between Nov/02-Jan/03, household contact was
made with 590 (61%), of which 487 (83%) completed the interview.
373/487 (77%) were aware of the program at the time of interview and
433 (89%) reported HBI, of whom 381/433 (88%) reportedly received
all 3 doses. Main parental reasons for non-HBI included concern about
side effects (26%), deferral to older age (23%), and perception that
their child was not at risk (11%). Statistically significant explanatory
variables for non-HBI included not having received any other
immunizations, lower levels of cues to action, and lower perceived
benefits of HBI. Parental-reported infant vaccine uptake and parental
awareness of HBI were high. Interventions that stimulate parents to
have their children vaccinated and that enhance parents’ understanding
of the benefits of immunization may improve infant immunization
coverage.
Injection Site Reactions to Booster Doses of Acellular Pertussis
Vaccine: Rate, Severity and Anticipated Impact
K. Pielak1, D. Skowronski1, V. Remple1, J. Macnabb1, D. Patrick1,
S. Halperin2, D. Scheifele3;
1University of British Columbia Centre for Disease Control, Vancouver, BC,
CANADA, 2Dalhousie University, Halifax, NS, CANADA, 3BC Children’s
Hospital, Vancouver, British Columbia, CANADA.
For primary doses, acellular-pertussis-combination vaccines cause
fewer adverse events than whole-cell-pertussis-combination vaccines.
However, evidence from clinical trials indicates booster doses may be
followed by extensive local reactions. This study compares the frequency,
severity and impact of local reactions amongst children receiving five
consecutive doses of an acellular-pertussis-combination vaccine, relative to
children receiving a mixed series of whole-cell followed by acellularcombination vaccines. Participants were caregivers of children aged 4-6
years, immunized at public health clinics across British Columbia,
Canada; this included 398 children receiving the fifth consecutive dose of
an acellular-pertussis-combination vaccine and 402 receiving the fifth
dose in a mixed regimen. Cross-sectional telephone survey assessed the
extent of local reactions 48-96 hours following immunization and their
impact on the child’s well-being. Children who received the fifth
consecutive dose of an acellular-pertussis-combination vaccine more often
experienced redness (24%) or swelling (16%) exceeding 46 mm than
children given a mixed series (10% and 9%, respectively; p=0.0007 and
p=0.003), but less often experienced tenderness or limitation of
movement at the injection site (p<0.0001 and p=0.02, respectively).
Related health care utilization was low. There was no effect on parental
attitudes toward vaccine; 90% would recommend the vaccine. Injection
site reactions are more extensive after fifth consecutive dose of an
acellular-pertussis-combination vaccine relative to a mixed regimen. These
reactions are unlikely to affect parental acceptance of immunization
recommendations.
65
Sixth Annual Conference
ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
P37
Orchitis Reported after Immunization.
V. Pool1, R. Pless2;
1Immunization Safety Branch, National Immunization Program/Centers for
Disease Control and Prevention, Atlanta, GA, 2Immunization and Respiratory
Infections Division, Health Canada, Ottawa, ON, CANADA.
Mumps was the leading infectious cause of orchitis and sterility in
the pre-vaccine era. Live measles-mumps-rubella vaccines (MMR) led to
a dramatic reduction of orchitis, however it was unclear whether the risk
still existed following vaccination. Case reports have been published, but
no adequate studies. Disproportionality analyses in the Vaccine Adverse
Event Reporting System (VAERS) found that orchitis was reported 2030 times more frequently following MMR than after any other vaccine.
We extended this assessment in VAERS of the possible risk of orchitis
following MMR. We searched VAERS (1990-2002) MMR reports using
coding terms EDEMA_GENITAL, ORCHITIS, EDEMA_SCROTUM,
TESTIS_DIS, EPIDIDYMITIS. These were reviewed, and a case-series
assembled; crude reporting rates were calculated using CDC vaccine
distribution data. Of 94 reports retrieved, 60 remained as possible cases
of orchitis. Ages ranged from 1 to 50 years, with 70% aged over 4. In 26,
orchitis was bilateral. In seven, parotitis preceded testicular symptoms. A
non-random distribution of symptom onset intervals was observed, with
peak at day 7-12. No sequelae were reported. Approximately 159 million
doses of MMR were distributed in the U.S. during the review period,
giving an estimated reporting rate of orchitis of 1 per 2,650,000 doses.
This is within the range reported from other countries. In the absence
of other reported causes and with plausible temporal relationships, some
of the cases we reviewed were likely due to MMR. However, even
accounting for possible underreporting, it appears that the risk of
orchitis and its sequelae is extremely small.
66
P38
A Pan-European Consortium for the Study on Autovaccination – A
Way to Combat the Most Common Pathogens/Infectious Diseases?
O. J. Nolte, The EURO-ATVo:CARD Consortium
Hygiene & Medical Microbiology, Hygiene-Institut, Heidelberg, GERMANY.
Autovaccines are immune modulating therapeutic vaccines, made
from a culture of a pathogen which has been isolated from the site of
infection. Autovaccination provides the opportunity to study in vivo
aspects of host-pathogen interaction if monitoring the patients response
to the autovaccine. However, only limited work has been spent on the
mechanism of action of autovaccines. Establishing a pan-European
consortium would permit the study of the effectiveness of
autovaccination for treatment of inflammatory processes, the effect these
autovaccines trigger on the immune system (innate/adaptive immunity)
and permit the use of the results for the development of therapeutic
vaccines against the most common pathogens (i.e., Staphylococcus aureus,
and others).
In June 2002, an expression of such interest was submitted to the
European Community to address the following objectives: (1)
consolidation of the consortium by inclusion of more groups with
diverse skills and expertise; (2) assessing the actual effectiveness of
autovaccination; (3) understanding the immune response following
application of autovaccines; (4) examination of host-pathogen
interaction; (5) identify antigens or virulence factors involved in hostpathogen interaction after autovaccination but not before (i.e. when the
patient suffered from disease) as vaccine candidates; and (6) integration
of these data into the development of preventative vaccines or modern
therapeutic vaccines which can then be used as an alternative to
antimicrobial drugs. The actual size of the consortium is 20 groups
from 7 different countries in Europe. The core groups of the consortium
started to work immediately after a kick-off conference held in Budapest
in November 2002.
on Vaccine Research
AUTHOR INDEX
Author
Abstract Number
Author
Abstract Number
Author
Abstract Number
Abdel-Messih, I. . . . . . . . . . . . . . . . .S11
Berman, J. . . . . . . . . . . . . . . . . . . . . .P10
Chikhlikar, P. R. . . . . . . . . . . . .P16, S15
Abramovitz, A. . . . . . . . . . . . . . . . . .S16
Bernstein, D. . . . . . . . . . . . . . . . . . . .S16
Cho, I. . . . . . . . . . . . . . . . . . . . . . . . .P18
Abu-Elyazeed, R. . . . . . . . . . . . . . . .S11
Bhargava, S. . . . . . . . . . . . . . . . . . . .S16
Choi, A. H. . . . . . . . . . . . . . . . . . . . .S30
Adamovicz, J. . . . . . . . . . . . . . . . . . . .S8
Bigham, M. . . . . . . . . . . . . . . . . . . . .P35
Choi, A. H. C. . . . . . . . . . . . . . . . . . .S31
Adams, M. M. . . . . . . . . . . . . . . . . . .P25
Bishop, E. A. . . . . . . . . . . . . . . . . . . .P15
Chu, Q. . . . . . . . . . . . . . . . . . . . . . . .P20
Adler-Moore, J. P. . . . . . . . . . . . . . . .P11
Biswas, S. . . . . . . . . . . . . . . . . . . . . .S40
Chumakov, K. . . . . . . . . . . . . . . . . . .S29
Adrian, P. . . . . . . . . . . . . . . . . . . . . . .P14
Bolin, C. A. . . . . . . . . . . . . . . . . . . . . .21
Chuprinina, R. P. . . . . . . . . . . . . . . . .S23
Allwine, D. A. . . . . . . . . . . . . . . . . . .P33
Bolt, C. . . . . . . . . . . . . . . . . . . . . . . . .S8
Clemens, J. . . . . . . . . . . . . . . . . . . . .S11
Alter, H. . . . . . . . . . . . . . . . . . . . . . .S39
Boudreau, E. . . . . . . . . . . . . . . . . . . .S10
Clements, J. D. . . . . . . . . . . . . . . . . . .S4
Alvarez, L. . . . . . . . . . . . . . . . . . . . .P31
Bouma, P. . . . . . . . . . . . . . . . . . . . . .S14
Clizbe, D. . . . . . . . . . . . . . . . . . . . . .S10
Alving, C. R. . . . . . . . . . . . . . . . . . . .P10
Brandt, B. L. . . . . . . . . . . . . . . . . . . .P10
Cochi, S. L. . . . . . . . . . . . . . . . . . . . . . .5
Amexis, G. . . . . . . . . . . . . . . . . . . . .S29
Brehm, M. . . . . . . . . . . . . . . . . . . . . . .31
Cole, K. S. . . . . . . . . . . . . . . . . . . . . .S19
Anderson, J. . . . . . . . . . . . . . . . . . . . .S8
Britz, J. A. . . . . . . . . . . . . . . . . . . . . . .P8
Connolly, E. . . . . . . . . . . . . . . . . . . . .P5
Anderson, R. M. . . . . . . . . . . . . . . . . . .3
Broder, C. . . . . . . . . . . . . . . . . . . . . .S14
Cosgrove, C. . . . . . . . . . . . . . . . . . . .S35
Andrianov, A. K. . . . . . . . . . . . . . . . .S30
Brunak, S. . . . . . . . . . . . . . . . . . . . . . .P1
Cramer, C. . . . . . . . . . . . . . . . . . . . . .P29
Angov, E. . . . . . . . . . . . . . . . . . . . . .P24
Brunham, R. C. . . . . . . . . . . . . . . . . .S32
Dagan, R. . . . . . . . . . . . . . . . . . . . . . . . .4
Anthony, L. S. D. . . . . . . . . . . . . . . .S18
Buist, G. . . . . . . . . . . . . . . . . . . . . . .P14
Dale, J. . . . . . . . . . . . . . . . . . . . . . . .S25
Aparin, P. G. . . . . . . . . . . . . . . . . . . .S23
Burt, D. . . . . . . . . . . . . . . . . . . . . . . . .S8
Daum, R. S. . . . . . . . . . . . . . . . . . . . . .17
Arruda, L. B. . . . . . . . . . . . . . . . . . . .P16
Byl, B. . . . . . . . . . . . . . . . . . . . . . . . . .P3
Davidson, C. . . . . . . . . . . . . . . . . . . . .S3
Artzen, C. . . . . . . . . . . . . . . . . . .P28, S5
Byrne, B. . . . . . . . . . . . . . . . . . . . . . .S15
Davies, G. . . . . . . . . . . . . . . . . . . . . . .P4
Babcock, J. . . . . . . . . . . . . . . . . . . . .P10
Caldwell, M. A. . . . . . . . . . . . . . . . . .S12
De Groot, A. S. . . . . . . . . . . . . . . . . .P15
Babiuk, L. . . . . . . . . . . . . . . . . . . . . .S32
Cannon, T. . . . . . . . . . . . . . . . . . . . . .S10
de Groot, R. . . . . . . . . . . . . . . . . . . . .P14
Babiuk, S. . . . . . . . . . . . . . . . . . . . . .S32
Carbone, K. . . . . . . . . . . . . . . . .P21, S29
De Serres, G. . . . . . . . . . . . . . . .S32, S33
Bailey, M. A. . . . . . . . . . . . . . . . . . . . .S7
Cardineau, G. . . . . . . . . . . . . . . . . . . .S5
De Wit, D. . . . . . . . . . . . . . . . . . . . . . .P4
Barouch, D. . . . . . . . . . . . . . . . . . . . .S28
Carpenter, C. C. J. . . . . . . . . . . . . . . .P15
Deepe, G. S. . . . . . . . . . . . . . . . . . . .S37
Barros de Arruda, L. . . . . . . . . . . . . .S15
Carucci, D. J. . . . . . . . . . . . . . . . . . . . .26
Dimitrov, D. . . . . . . . . . . . . . . . . . . .S14
Basu, M. . . . . . . . . . . . . . . . . . .S30, S31
Cassels, F. . . . . . . . . . . . . . . . . . . . . .S22
Dionne, M. . . . . . . . . . . . . . . . . . . . .S33
Bauer, J. . . . . . . . . . . . . . . . . . . . . . . .P3
Castello-Branco, L. . . . . . . . . . . . . . .S35
Dobrogosz, W. J. . . . . . . . . . . . . . . . . .P5
Beenhouwer, D. O. . . . . . . . . . . . . . .S38
Chao-Hong Hu, M. . . . . . . . . . . . . . .S25
Duncan, E. H. . . . . . . . . . . . . . . . . . .P24
Belkaid, Y. . . . . . . . . . . . . . . . . . . . . . .16
Chaulk, C. . . . . . . . . . . . . . . . . . . . . .S16
Duval, B. . . . . . . . . . . . . . . . . . . . . . .S33
Bell, S. J. D. . . . . . . . . . . . . . . . . . . . .P4
Chen, D. . . . . . . . . . . . . . . . . . . . . . .P20
Eibner, J. . . . . . . . . . . . . . . . . . . . . . . .S6
Bellini, W. . . . . . . . . . . . . . . . . . . . . .S28
Chen, J. . . . . . . . . . . . . . . . . . . . . . . .S30
El-Mohamady, H. . . . . . . . . . . . . . . .S11
Bergmann-Leitner, E. S. . . . . . . . . . .P24
Chiavaroli, C. . . . . . . . . . . . . . . . . . . .P3
Elkina, S. I. . . . . . . . . . . . . . . . . . . . .S23
67
Sixth Annual Conference
AUTHOR INDEX
Author
Abstract Number
Author
Abstract Number
Author
Abstract Number
Ernst, W. A. . . . . . . . . . . . . . . . . . . . .P11
Harris, A. M. . . . . . . . . . . . . . . . . . . .S17
Kirk, D. D. . . . . . . . . .P28, P30, P31, S6
Estafao, S. . . . . . . . . . . . . . . . . . . . . .P14
Harris, R. . . . . . . . . . . . . . . . . . . . . . .S36
Klein, B. S. . . . . . . . . . . . . . . . . . . . .S37
Eyre, P. . . . . . . . . . . . . . . . . . . . . . . .P26
Hart, M. . . . . . . . . . . . . . . . . . . . . . . . .S9
Kok, J. . . . . . . . . . . . . . . . . . . . . . . .P14
Fanton, M. . . . . . . . . . . . . . .P28, S5, S5
Hartman, A. . . . . . . . . . . . . . . . . . . . .S22
Koopman, J. S. . . . . . . . . . . . . . . . . .S20
Fattom, A. I. . . . . . . . . . . . . . . . . . . .S26
Hayglass, K. . . . . . . . . . . . . . . . . . . .S32
Koprowski, H. . . . . . . . . . . . . . . . . . . .S1
Feng, Y. . . . . . . . . . . . . . . . . . . . . . . .S36
Hayney, M. S. . . . . . . . . . . . . . . . . . .P19
Kortepeter, M. . . . . . . . . . . . . . . . . . .S10
Filutowicz, H. I. . . . . . . . . . . . . . . . .S37
He, Q. . . . . . . . . . . . . . . . . . . . . . . . . .P4
Kotloff, K. L. . . . . . . . . . . . . . . . . . . . .20
Fohl, R. M. . . . . . . . . . . . . . . . . . . . .P19
Heinrich, J. . . . . . . . . . . . . . . . . . . . .P32
Kowalski, J. . . . . . . . . . . . . . . . . . . . .S16
Foti, S. . . . . . . . . . . . . . . . . . . . . . . . .P15
Hermans, P. . . . . . . . . . . . . . . . . . . . .P14
Kowalski, R. J. . . . . . . . . . . . . . . . . . .P8
Franco, J. . . . . . . . . . . . . . . . . . . . . . .P15
Hesley, T. M. . . . . . . . . . . . . . . . . . . .S21
Kuipers, O. . . . . . . . . . . . . . . . . . . . .P14
Frenck, R. . . . . . . . . . . . . . . . . . . . . .S11
Hinds, P. W. . . . . . . . . . . . . . . . . . . . .P13
L’vov, V. L. . . . . . . . . . . . . . . . . . . . .S23
Friedlander, A. M. . . . . . . . . . . . . . . . . .7
Hirunpetcharat, C. . . . . . . . . . . . . . . .S34
Lackemeyer, M. . . . . . . . . . . . . . . . . .S9
Fuller, S. . . . . . . . . . . . . . . . . . . . . . .S26
Hoffenbach, A. . . . . . . . . . . . . . . . . .S21
Lally, M. . . . . . . . . . . . . . . . . . . . . . .P15
Fuller, T. . . . . . . . . . . . . . . . . . . . . . .S33
Hopkins, R. J. . . . . . . . . . . . . . . . . . .S12
Landry, S. J. . . . . . . . . . . . . . . . . . . . . .30
Funk, V. . . . . . . . . . . . . . . . . . . . . . .P29
Horwith, G. . . . . . . . . . . . . . . . . . . . .S26
Langley, J. . . . . . . . . . . . . . . . . . . . . .S25
Gallagher, P. . . . . . . . . . . . . . . . . . . . .S9
Howe, R. C. . . . . . . . . . . . . . . . . . . . .S27
Langley, J. M. . . . . . . . . . . . . . . . . . .S21
Gangolli, S. . . . . . . . . . . . . . . . . . . . .S16
Jackson, W. J. . . . . . . . . . . . . . .S17, S36
Lanzavecchia, A. . . . . . . . . . . . . . . . . . .1
Gantcho, T. V. . . . . . . . . . . . . . . . . . .S23
Jacobsen, K. . . . . . . . . . . . . . . . . . . .S33
Leavitt, M. . . . . . . . . . . . . . . . . . . . . .S14
Giemza, R. . . . . . . . . . . . . . . . . . . . .S35
Jacobson, S. H.
. . . . . . . . . . . . . . . .P34
Lee, L. F. . . . . . . . . . . . . . . . . . . . . . .P12
Gilliam, S. . . . . . . . . . . . . . . . . . . . . .S3
Jin, Y. . . . . . . . . . . . . . . . . . . . . . . . . .P31
Lee, Y. . . . . . . . . . . . . . . . . . . . . . . . .S11
Goldman, M. . . . . . . . . . . . . . . . . . . . .P4
Johnson, K. L. . . . . . . . . . . . . . . . . . .S27
Leenhouts, K. . . . . . . . . . . . . . . . . . .P14
Golovina, M. E. . . . . . . . . . . . . . . . . .S23
Jones, T. . . . . . . . . . . . . . . . . . . . . . . .S8
Leong, K. W. . . . . . . . . . . . . . . . . . . .S13
Good, M. F. . . . . . . . . . . . . . . . . . . . .S34
Julander, J. G. . . . . . . . . . . . . . . . . . .S18
Letvin, N. . . . . . . . . . . . . . . . . . . . . .S28
Gopinath, E. . . . . . . . . . . . . . . . . . . .P18
Kamal, K. . . . . . . . . . . . . . . . . . . . . .S11
Lewis, A. . . . . . . . . . . . . . . . . . .P17, P18
Graham, B. S. . . . . . . . . . . . . . . . . . . . .8
Kaminski, R. W. . . . . . . . . . . . . . . . .P12
Lewis, D. . . . . . . . . . . . . . . . . . . . . . .S35
Grandinetti, T. . . . . . . . . . . . . . . . . . .S39
Kango, R. . . . . . . . . . . . . . . . . . . . . .P13
Lewis, M. . . . . . . . . . . . . . . . . . . . . .S15
Greenberg, R. N. . . . . . . . . . . . . . . . .S12
Kanninga, R. . . . . . . . . . . . . . . . . . . .P14
Libin, M. . . . . . . . . . . . . . . . . . . . . . . .P4
Griffin, G.E. . . . . . . . . . . . . . . . . . . .S35
Karasev, A. V. . . . . . . . . . . . . . . . . . . .S1
Lin, X. . . . . . . . . . . . . . . . . . . . . . . . .S20
Guay, M. . . . . . . . . . . . . . . . . . . . . . .S33
Karnani, T. . . . . . . . . . . . . . . . . . . . .P34
Lind, C. . . . . . . . . . . . . . . . . . . . . . . . .S9
Guerry, P. . . . . . . . . . . . . . . . . . . . . . .P12
Karron, R. A. . . . . . . . . . . . . . . . . . . . .19
Liu, H. . . . . . . . . . . . . . . . . . . . . . . . .S18
Hall, E. . . . . . . . . . . . . . . . . . . . . . . .S11
Keefe, R. G. . . . . . . . . . . . . . . . . . . .S36
Liu, S. . . . . . . . . . . . . . . . . . . . . . . . .S13
Halperin, S. A. . . . . . . . . .S21, S25, P37
Kerr, P. J. . . . . . . . . . . . . . . . . . . . . . .P25
Long, D. . . . . . . . . . . . . . . . . . . . . . .S16
Hargis, D. L. . . . . . . . . . . . . . . . . . . .S12
Khan, F. . . . . . . . . . . . . . . . . . . . . . . .P24
Lowell, G. . . . . . . . . . . . . . . . . . . . . . .S8
68
on Vaccine Research
AUTHOR INDEX
Author
Abstract Number
Author
Abstract Number
Author
Abstract Number
Lu, H. . . . . . . . . . . . . . . . . . . . . . . . .S17
Mizzen, L. A. . . . . . . . . . . . . . . . . . .S18
Pitt, M. . . . . . . . . . . . . . . . . . . . . . . . .S8
Lu, S. . . . . . . . . . . . . . . . . . . . . . . . . .S40
Montaner, A. D. . . . . . . . . . . . . . .P6, P7
Pittner, B. . . . . . . . . . . . . . . . . . . . . .S11
Lund, O. . . . . . . . . . . . . . . . . . . . . . . .P1
Montelaro, R. C. . . . . . . . . . . . . . . . .S19
Pless, R. . . . . . . . . . . . . . . . . . . . . . .P37
Lundegaard, C. . . . . . . . . . . . . . . . . . .P1
Moran, E. E. . . . . . . . . . . . . . . . . . . .P10
Pletnikov, M. . . . . . . . . . . . . . . . . . .S29
Lyon, J. A. . . . . . . . . . . . . . . . . . . . . .P24
Morcol, T. . . . . . . . . . . . . . . . . . . . . . .P4
Plummer, B. A. . . . . . . . . . . . . . . . . .S12
Maciel Jr, M. . . . . . . . . . . . . . . . . . . .S15
Morrey, J. D. . . . . . . . . . . . . . . . . . . .S18
Poland, G. A. . . . . . . . . . . . . . . . . . . .S27
Maciel Jr., M. . . . . . . . . . . . . . . . . . .P16
Morrill, J. C. . . . . . . . . . . . . . . . . . . . .22
Pool, V. . . . . . . . . . . . . . . . . . . . . . . .P37
Macnabb, J. . . . . . . . . . . . . . . . . . . . .P36
Morsy, B. . . . . . . . . . . . . . . . . . . . . . .S11
Pratt, W. . . . . . . . . . . . . . . . . . . . . . . . .S9
Major, J. L. . . . . . . . . . . . . . . . . . . . .P32
Moyer, P. . . . . . . . . . . . . . . . . . . . . . .S11
Premenko-Lanier, M. F. . . . . . . . . . .S28
Mann, B. . . . . . . . . . . . . . . . . . . . . . .P29
Muddiman, D. C. . . . . . . . . . . . . . . .S27
Putnam, S. . . . . . . . . . . . . . . . . . . . . .S11
Mann, D. . . . . . . . . . . . . . . . . . . . . . . .S3
Muller, D. . . . . . . . . . . . . . . . . . . . . .P19
Qiu, Q. . . . . . . . . . . . . . . . . . . . . . . .S39
Marques Jr., E. T. A. . . . . . . . . . . . . .P16
Murphey-Corb, M. . . . . . . . . . . . . . .S19
Quinnan, G. . . . . . . . . . . . . . . . . . . . .S14
Martin, O. . . . . . . . . . . . . . . . . . . . . . .P4
Nabors, G. S. . . . . . . . . . .P13, S17, S36
Radley, D. . . . . . . . . . . . . . . . . . . . . .S21
Martin, W. . . . . . . . . . . . . . . . . . . . . .P15
Nagappan, P. R. . . . . . . . . . . . . . . . . . .P4
Ranallo, R. T. . . . . . . . . . . . . . . . . . .S22
Mason, H. . . . . . . . . . . . . . . . . . . . . . .S6
Naso, R. . . . . . . . . . . . . . . . . . . . . . . .S26
Rao, K. V. S. . . . . . . . . . . . . . . . . . . . .28
Mason, H. S. . . . . . . . . . . . .P28, P30, S5
Nerenbaum, L. . . . . . . . . . . . . . . . . . .P4
Rao, M. . . . . . . . . . . . . . . . . . . . . . . .S11
Matijevic, M. I. . . . . . . . . . . . . . . . . . .P9
Ni, Y. . . . . . . . . . . . . . . . . . . . . . . . . . .P3
Recktenwald, A. . . . . . . . . . . . . . . . .S18
Mauldin, J. P. . . . . . . . . . . . . . . . . . .P21
Nielsen, M. . . . . . . . . . . . . . . . . . . . . .P1
Reddish, M. . . . . . . . . . . . . . . . . . . . .S25
May, R. J. . . . . . . . . . . . . . . . . . . . . .S38
Nolte, O. J. . . . . . . . . . . . . . . . .P27, P38
Reddy, J. . . . . . . . . . . . . . . . . . .P17, P18
Mayer, K. H. . . . . . . . . . . . . . . . . . . .P15
Norris, S. . . . . . . . . . . . . . . . . . . . . . .S10
Reed, D. S. . . . . . . . . . . . . . . . . . . . . .S9
McChesney, M. . . . . . . . . . . . . . . . . .S28
Oaks, E. V. . . . . . . . . . . . . . . . . . . . . .P12
Remple, V. P. . . . . . . . . . . . . . . . .P35, 37
McIntyre, C. . . . . . . . . . . . . . . . . . . .P35
Ovsyannikova, I. G. . . . . . . . . . . . . .S27
Rhodes, G. . . . . . . . . . . . . . . . . . . . . .S28
McIver, L. Y. A. . . . . . . . . . . . . . . . . .P32
Pan, A. . . . . . . . . . . . . . . . . . . .P22, P23
Rigano, M. . . . . . . . . . . . . . . . . . . . .P31
McNeal, M. M. . . . . . . . . . . . . .S30, S31
Paradiso, P. R. . . . . . . . . . . . . . . . . . . .12
Roberts, S. A. . . . . . . . . . . . . . . . . . .S12
McNeil, S. . . . . . . . . . . . . . . . . . . . . .S25
Parker, M. . . . . . . . . . . . . . . . . . . . . . .S9
Robillard, G. . . . . . . . . . . . . . . . . . . .P14
McVetty, T. . . . . . . . . . . . . . . . . . . . . .S3
Pasquier, F. . . . . . . . . . . . . . . . . . . . .P32
Robinson, J. . . . . . . . . . . . . . . . . . . . .S14
Medina, E. A. . . . . . . . . . . . . . . . . . .P33
Patrick, D. . . . . . . . . . . . . . . . . . . . . .P36
Rochette, L. . . . . . . . . . . . . . . . . . . . .S33
Medina-Bolivar, F. . . . . . . . . . . . . . .P29
Pavlova, L. I. . . . . . . . . . . . . . . . . . . .S23
Rosenthal, A. . . . . . . . . . . . . . . . . . . .P11
Mehta, H. . . . . . . . . . . . . . . . . .P17, P18
Petri Jr., W. . . . . . . . . . . . . . . . . . . . .P29
Rota, P. . . . . . . . . . . . . . . . . . . . . . . .S28
Mett, V. . . . . . . . . . . . . . . . . . . . . . . . .S3
Pham, J. . . . . . . . . . . . . . . . . . . .P17, P18
Rowland, L. . . . . . . . . . . . . . . . . . . . .P31
Miller, T. J. . . . . . . . . . . . . .P28, P30, S5
Pielak, K. . . . . . . . . . . . . . . . . .P35, P36
Rowles, J. L. . . . . . . . . . . . . . . . . . . .S19
Mills, K. H. G. . . . . . . . . . . . . . . . . . . .15
Pier, G. B. . . . . . . . . . . . . . . . . . . . . . .18
Rowse, G. . . . . . . . . . . . . . . . . . . . . .S18
Milstien, J. B. . . . . . . . . . . . . . . . . . . .10
Pillai, S. . . . . . . . . . . . . . . . . . . . . . . .P23
Rubin, S. . . . . . . . . . . . . . . . . . . . . . .P21
Mitchell, A. R. . . . . . . . . . . . . . . . . . . .P4
Pinkhasov, J.
Rubin, S. A. . . . . . . . . . . . . . . . . . . . .S29
. . . . . . . . . . . . . . . . . .P31
69
Sixth Annual Conference
AUTHOR INDEX
Author
Abstract Number
Author
Abstract Number
Author
Abstract Number
Rupprecht, C. E. . . . . . . . . . . . . . . . . .23
Strasser, J. . . . . . . . . . . . . . . . . . . . . .S16
Webb, S. R. . . . . . . . . . . . . . . . . . . . .P28
Rusnak, J. M. . . . . . . . . . . . . . . . . . .S10
Streatfield, S. J. . . . . . . . . . . . . . . . . . .S4
Weekley, B. . . . . . . . . . . . . . . . . . . . .P26
Ryan, J. E. . . . . . . . . . . . . . . . . . . . . .S27
Stroop, S. . . . . . . . . . . . . . . . . . . . . . .S25
Weiner, D. B. . . . . . . . . . . . . . . . . . . .P15
Saiki, T. . . . . . . . . . . . . . . . . . . . . . . .P32
Stroup, S. . . . . . . . . . . . . . . . . . . . . . .P29
Weiss, H. E. . . . . . . . . . . . . . . . . . . .P27
Sathiyaseelan, J. . . . . . . . . . . . . . . . . .P9
Svennerholm, A. . . . . . . . . . . . . . . . .S11
Weiss, R. . . . . . . . . . . . . . . . . . . . . . .P24
Saul, A. . . . . . . . . . . . . . . . . . . . . . . . .27
E.T.A. Marques, Jr. . . . . . . . . . . . . . .S15
Wen, J. . . . . . . . . . . . . . . . . . . . . . . . .S13
Savarino, S. . . . . . . . . . . . . . . . . . . . .S11
Tacket, C. O. . . . . . . . . . . . . . . . . . . . .S4
Weniger, B. G. . . . . . . . . . . . . . . . . . .P33
Sbai, H. . . . . . . . . . . . . . . . . . . . . . . .P15
Tain, J. . . . . . . . . . . . . . . . . . . . . . . . .S36
Wheelis, M. . . . . . . . . . . . . . . . . . . . . . .6
Scharff, M. D. . . . . . . . . . . . . . . . . . .S38
Taylor, L. . . . . . . . . . . . . . . . . . . . . . .S39
White, R. . . . . . . . . . . . . . . . . . . . . . .P35
Scheiblhofer, S. . . . . . . . . . . . . . . . . .P24
Thalhamer, J. . . . . . . . . . . . . . . . . . . .P24
White, W. . . . . . . . . . . . . . . . . . . . . .P18
Scheifele, D. . . . . . . . . . . . . . . . . . . .P36
Thomas J. . . . . . . . . . . . . . . . . .P16, S15
Wierzba, T. . . . . . . . . . . . . . . . . . . . .S11
Schweighofer, K. . . . . . . . . . . . . . . .P17
Tian, L. . . . . . . . . . . . . . . . . . . . . . . . .P2
Wigdorovitz, A. . . . . . . . . . . . . . . . . . .S2
Scissum-Gunn, K. . . . . . . . . . . . . . . .P23
Tizard, I. . . . . . . . . . . . . . . . . . . . . . . .P2
Willems, F. . . . . . . . . . . . . . . . . . . . . .P3
Scott, D. . . . . . . . . . . . . . . . . . . . . . .P12
Tomer, K. B. . . . . . . . . . . . . . . . . . . . .29
Winslow, S. G. . . . . . . . . . . . . . . . . .S18
Sedegah, M. . . . . . . . . . . . . . . . . . . .P22
Tsokos, G. . . . . . . . . . . . . . . . . . . . . .P24
Winston, S. . . . . . . . . . . . . . . . . . . . .S26
Sewell, E. C. . . . . . . . . . . . . . . . . . . .P34
Turbyfill, K. R. . . . . . . . . . . . . . . . . .P12
Winter, D. . . . . . . . . . . . . . . . . . . . . .P24
Sexton, A. . . . . . . . . . . . . . . . . . . . . .S35
Urban, R. G. . . . . . . . . . . . . . . . . . . . .P9
Wipasa, J. . . . . . . . . . . . . . . . . . . . . .S34
Shevach, E. M. . . . . . . . . . . . . . . . . . .14
van Alphen, L. . . . . . . . . . . . . . . . . . .S24
Woodcock, J. B. . . . . . . . . . . . . . . . . .P8
Shih, J. . . . . . . . . . . . . . . . . . . . . . . . .S39
van den Dobbelsteen, G. . . . . . . . . .S24
Worning, P. . . . . . . . . . . . . . . . . . . . . .P2
Shmigol, V. I. . . . . . . . . . . . . . . . . . .S23
van der Zeijst, B. . . . . . . . . . . . . . . . .S24
Wright, R. . . . . . . . . . . . . . . . . . . . . .P29
Siegel, M. I. . . . . . . . . . . . . . . . . . . . .S18
van Leeuwen, B. H. . . . . . . . . . . . . . .P25
Wu, B. &tab . . . . . . . . . . . . . . . . . . .S18
Silber, J. L. . . . . . . . . . . . . . . . . . . . .S21
van Roosmalen, M. . . . . . . . . . . . . . .P14
Wu, W. . . . . . . . . . . . . . . . . . . . . . . . .P35
Silvera, P. . . . . . . . . . . . . . . . . . . . . .S15
Veerman, T. F. A. . . . . . . . . . . . . . . . .S24
Wuethrich, M. . . . . . . . . . . . . . . . . . .S37
Singh, S. . . . . . . . . . . . . . . . . . . . . . .P23
Veit, H. . . . . . . . . . . . . . . . . . . . . . . .P26
Xu, H. . . . . . . . . . . . . . . . . . . . . . . . .S34
Skowronski, D. . . . . . . . . .P36, S32, S33
Venkatesan, M. . . . . . . . . . . . . . . . . .S22
Xu, J. . . . . . . . . . . . . . . . . . . . . .P17, P18
Smith, B. . . . . . . . . . . . . . . . . . . . . . .S25
Vink, P. . . . . . . . . . . . . . . . . . . . . . . .S25
Yates, K. M. . . . . . . . . . . . . . . . . . . . .P3
Smith, L. . . . . . . . . . . . . . . . . . . . . . .S10
Vonhof, W. . . . . . . . . . . . . . . . . . . . . .S6
Ye, M. . . . . . . . . . . . . . . . . . . . . . . . .P32
Song, R. . . . . . . . . . . . . . . . . . . . . . . .S13
Walker, R. I. . . . . . . . . . . . . . . . . . . .S36
Yolken, R. . . . . . . . . . . . . . . . . . . . . .P21
Soni, J. . . . . . . . . . . . . . . . . . . .P17, P18
Walmsley, A. M. . . . . . . . . . . . .P30, P31
Yusibov, V. M. . . . . . . . . . . . . . . . . . . .S3
Spangler, L. . . . . . . . . . . . . . . . . . . . .P32
Wang, R. . . . . . . . . . . . . . . . . . . . . . .S39
Zamb, T. . . . . . . . . . . . . . . . . . . . . . .S16
Sra, K. . . . . . . . . . . . . . . . . . . . .P17, P18
Ward, R. L. . . . . . . . . . . . . . . . .S30, S31
Zappacosta, P. S. . . . . . . . . . . . . . . . .S21
Sriranganathan, N. . . . . . . . . . . . . . .P26
Warner, T. . . . . . . . . . . . . . . . . . . . . .S37
Zhang, X. . . . . . . . . . . . . . . . . . . . . . .S6
Steen, A. . . . . . . . . . . . . . . . . . . . . . .P14
Wassef, N. M. . . . . . . . . . . . . . . . . . .P10
Zolla-Pazner, S. . . . . . . . . . . . . . . . . .S14
Stowers, A. . . . . . . . . . . . . . . . . . . . .S34
Wasserman, S. S. . . . . . . . . . . . . . . . . .S4
Zollinger, W. D. . . . . . . . . . . . . . . . .P10
70
on Vaccine Research
DISCLOSURE INDEX
As a sponsor accredited by the Accreditation Council of Continuing Medical Education (ACCME) the
National Foundation for Infectious Diseases must insure balance, independence, objectivity, and scientific
rigor in all its individually sponsored or jointly sponsored educational activities. All faculty participating in a
sponsored activity and all Scientific Program Committee Members are expected to disclose to the activity
audience: (1) any significant financial interest or other relationship (a) with the manufacturer(s) of any
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speakers bureau, etc.); and (2) any intention to discuss off-label uses of regulated substances or devices.
The intent of this disclosure is not to prevent a speaker, nor a Scientific Program Committee member, with a
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but rather to provide listeners with information on which they can make their own judgments. It remains for
the audience to determine whether the speaker’s interests or relationships may influence the presentation with
regard to exposition or conclusion.
The following Presenters have no relationships to disclose:
Adams, M.
Bailey, M.A.
Belkaid, Y
BergmannLeitner, E.S.
Brehm M.
Carucci, D.J.
Chen, D.
Chikhilikar, P.R.
Cochi, S.L.
Cosgrove, C.
Dhiman, N.
Friedlander, A.M.
Graham, B.S.
Guerrero, R.B.
Hill, A.
Haney, M.S.
Jacobson, S.H.
Kaminski, R.W.
Karasev, A.V.
Koopman, J.S.
Leavitt, M.
Leenhouts, K.
Long, D.
Lu, S.
Lund, O
Major J.L.
Marques, E.T.A.
Mauldin, J.P.
May, R.J.
Medina-Bolivar, F.
Milstien, J.B.
Morrill, J.D.
Nagappan, P.
Ni, Y.
Nolte, O.J.
Ovsyannikova, I.G.
Pielak, K.
Pool, V.
Premenko-Lanier, M.F.
Ranallo, R.T.
Rao, K.V.S.
Reed, D.S.
Remple, V.P.
Rosenthal, A.
Rowles, J.L.
Rubin, S.A.
Rupprecht, C.E.
Rusnak, J.M.
Saul, A.
Savarino, S.
Sedegah, M.
Shevach, E.M.
Singh, S.
Song, R.
Tacket, C.O.
Tomer, K.B.
Van Alphen, L.
Wang, R.
Wigdorovitz, A.
Woodcock, J.B.
Wuethrich, M.
Xu, H.
Yusibov, V.M.
Zollinger, W.
The following Program Committee Members have no relationships to disclose:
McInnes, P.
Nara, P.
Neumann, D.
Rabinovich, R.
Robinson, H.
Schmaljohn, C.
The remaining Presenters have disclosed the following:
Presenter
Company
Relationship*
Anderson, R.
Anthony, L.S.D.
Aparin, P.G.
Bolin, C.A.
Abbott Laboratories
Stressgen Biotechnologies, Corp.
ATV D-Team Company, Ltd.
Pfizer Animal Health, Fort
Dodge Animal Health
Parrallel Solutions, Inc.
B, E
A, C
C
Choi, A.H.
E
B
71
Sixth Annual Conference
DISCLOSURE INDEX
Presenter
Company
Relationship*
Dagan, R.
Abbott, Aventis, Bayer, Biotechnology General
Bristol Myers-Squibb, Eli-Lilly, GSK,
Johnson & Johnson, Marion-Merrell-Dow
Merck, Pfizer, Roche, Schering-Plough
Wyeth, Zeneca
OM Pharmaceuticals
Aventis,
BioGaia
Nabi Biopharmaceuticals
Dynport
Merck
ID Biomedical Corp of Quebec
Wyeth Vaccines
Antex Biologics, Inc.
Dow AgroSciences
Lacticulture, Inc.
Antex Biologics, Inc.
Zycos, Inc.
Austral Engineering and Software, Inc.
Benchmark Biolabs, Inc.
Immunotech
Antex Biologics, Inc.
MedImmune Vaccines
Wyeth Pharmaceuticals
Binax, Inc.
NIH (R01 AI 50528)
Aventis Pasteur
MedImmune Vaccines
Biomedical of Marylanc
Avant
AgroSciences
Merck and Company, Inc.
E
C
E
A, B
C
B
B
A, C.
B
C
B
B, D
C
A
C, D
C
B
C
A, C
C
E
B
B
A, C
A, C
G
C
C
Davies, G.
De Serres, G.
Dobrogosz, W.J.
Fattom, A.I.
Greenberg, R.N.
Halperin, S.
Jones, T.
Karron, R.A.
Keefe, R.
Kirk, D.D.
Landry S.J.
Lu, H.
Matijevic, M.I.
Medina, E.A.
Miller, T.J.
Montaner, A.D.
Nabors G.S.
Pan, A.
Paradiso, P.R.
Pier, G.B.
Sbai, H.
Skowronski, D
Sra, K
Vink, P.
Ward, R.L.
Webb, S.R.
Weekley, B.
The remaining Program Committee Members disclosed the following:
Griffin, D.
Henri-Lambert, P.
Plotkin, S.
Rappuoli, R.
Shevach, E.
Siber, G.
Swayne, D.
Weniger, B.
Banchereau, J.
Poland
72
Becton Dickinson, MedImmune, Merck
GSK, Aventis Pasteur, Chiron, OM-Pharma
Aventis Pasteur
Chiron
Tanox, Inc., Vaccinex, Aventis,
Abbott, Wyeth
Wyeth
Merial, Inc.
VaxGen
Merix BioScience
Merck & Co, Inc.
B, E
E
E
C
E
C
B
C
B
B
on Vaccine Research
DISCLOSURE INDEX
*Please refer to the following relationship table
Label
Relationship
A
I have stocks, stock options, and/or bond holdings in this company
B
I have a research grant, stipend, and/or fellowship from this company
C
I am employed by this company, or it employs a member of my immediate family
D
I or a member of my immediate family own or is a partner in this company
E
I or a member of my immediate family receive consulting fees, honoraria, paid meeting
registration fees, paid travel, speaking fees, or other financial compensation from this company
F
I or a member of my immediate family hold a nonrenumerative position of influence with this
company such as officer, board member, trustee, or public spokesperson.
G
I or a member of my immediate hold a patent for and/or receive royalties from this company’s
product
73