Inactivated Influenza Vaccine
Administration via Microneedle
Patch; a Novel Vaccine Delivery
System
Karen Mask, RN, BSN
MPH Candidate
April 11, 2014
Background
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Seasonal influenza leads to significant morbidity &
mortality each year.
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Worldwide:
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United States:
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3 to 5 million cases of severe illness
250,000 to 500,000 deaths per year (WHO, 2009)
>220,000 hospitalizations
36,000 deaths per year (Thompson, 2004)
Vaccination is the most effective way of preventing
influenza.
CDC recommends annual flu vaccine for everyone 6
months and older
Background

Despite recommendations, early season vaccination coverage
was only 39.5% for 2013-2014 flu season (CDC, 2013)
http://www.cdc.gov/flu/fluvaxview/nifs-estimates-nov2013.htm
Background
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Barriers to flu vaccination
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Needle phobia
Access to vaccine
Vaccine acceptability
Need for trained personnel to administer vaccine
Lack of financial and physical space resources
Background
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Microneedle patches
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Micron-scale (10-6 m) needles, minimally invasive,
eliminate sharps waste, painless
http://drugdelivery.chbe.gatech.edu/gallery_microneedles.html
Background

Microneedle patch product administration
http://drugdelivery.chbe.gatech.edu/Images/Image_gallery/Full/patch-application.jpg
Background
Microneedle patch pre-clinical studies
 Mice model microneedle study (Zhu et al, 2009)
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Vaccinated with H1N1 and H3N2 strains via microneedle
patch
Protected when challenged with lethal flu dose
Rabies, BCG, HPV vaccine studies
Favorable safety profile to date
Acceptability study (Norman et al, 2014)
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increased intent to vaccinate with microneedle
patches (from 44% to 65%)
majority preference to self-vaccinate (64%)
Rationale
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Flu vaccination is highly effective in preventing
disease but barriers to vaccination limit the
protective impact of influenza vaccination programs.
Microneedle patch delivery system has potential to
greatly impact acceptability and ease of delivery of
inactivated flu vaccine.
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Painless, simple administration
Effect more profound in pandemic flu situation
Potential to expand beyond influenza vaccine.
Reduction in influenza related morbidity & mortality
Internship
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The Hope Clinic of the
Emory Vaccine Center;
Emory University

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National Institutes of Health
(NIH) funded Vaccine
Treatment and Evaluation
Unit (VTEU)
Preceptor – Dr. Nadine
Rouphael
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Assistant Professor
Department of Medicine,
Division of Infectious
Diseases, Emory University
School of Medicine
Special Project

A Phase I Study of the Safety, Reactogenicity,
Acceptability and Immunogenicity of Inactivated
Influenza Vaccine Delivered by Microneedle Patch
or by Hypodermic Needle
(working title - in development)
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Microneedle technology – Dr. Mark Prausnitz
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Clinical trial development and execution –
Drs. Nadine Rouphael and Mark Mulligan
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Sponsored by: National Institute of Biomedical Imaging
and Bioengineering (NIBIB)
Objectives
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Project Development
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Establish collaborative working group
Microneedle team develop concept
Clinical team develop clinical trial protocol
Secure Investigational New Drug (IND) approval
Secure Institutional Review Board (IRB) approvals
Complete clinical trial preparation
Clinical Trial
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Evaluate safety and reactogenicity of study product
Evaluate immunogenicity of study product
Compare immunogenicity of staff vs. self administration
Methods
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Literature search
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CDC Ecological Framework
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Morbidity & mortality of influenza, microneedle
development and testing, public health programs and
roadblocks
Individual factors (needle phobia) 
Relationship factors (family members decline vaccine) 
Community factors (herd immunity) 
Societal factors (policy)
Policy analysis
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Vaccination recommendations vs. requirements
Methods
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Financial management
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Grant funding coverage and restrictions
Program planning & evaluation
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Clinical trial design: subject recruitment, blinding,
statistical significance
Results analysis – safety, reactogenicity, immunogenicity
Results
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Established collaborative working group
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Microneedle development team at Georgia Tech led by
Dr. Mark Prausnitz
Clinical trial development team at Emory University led
by Dr. Nadine Rouphael
Team conference calls and in-person development
meetings
Microneedle patch concept developed by Georgia
Tech
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Delivered to Emory University for study protocol
development
Results
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Emory clinical trial team developed draft study
design and protocol
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Progress towards securing IND / IRB approvals
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Delivered to Georgia Tech for review and pre-IND
submission
Pre-IND meeting held; study team incorporating FDA
comments in protocol and preparing FDA response
Working on final IND submissions
Complete clinical trial preparation – Fall 2014/Spring
2015
Clinical trial – Spring/Summer 2015
Results - Timeline
Pre-June 2013
Concept
Development
Collaborative
Group
Protocol
Development
IND
Application
Clinic
Preparations
Clinical
Trial
Summer 2013
Spring 2014
Summer 2014
Fall 2014
Spring 2015
Winter 2015
Discussion
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Microneedle technology is very early in development
A project of this scope takes several years to
develop, implement and analyze the results
Front end of the project is primarily administrative,
but critical to achieving accurate, reliable, and
generalizable data
As a first-in-humans trial, this protocol will need to
be replicated and/or expanded to ensure results are
accurate and generalizable.
Implications
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Improved acceptability of annual influenza
vaccination
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Pain reduction, improved access to vaccine, potential for
self-vaccination
Increased compliance to annual influenza
vaccination recommendations
Potential decreased influenza morbidity and
mortality through improved immunogenicity of
intradermal vaccination
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Targets antigen-presenting Langerhans and dermal
dendritic cells.
Implications
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Potential for improved and expanded global vaccination
program (provided methods are generalizable to other
vaccines)
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Improved access to vaccine
Improved vaccine stability and less stringent cold chain
requirements
Decreased reliance on administration by trained personnel
Increased acceptability
Expansion of collaborative partnerships across
concentration areas such as engineering and healthcare
MPH Core Competencies Strengthened
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Monitoring health status to identify and solve
community health problems
Mobilizing community partnerships and action to
identify and solve health problems
Evaluating effectiveness, accessibility and quality of
personal and population-based health services
Conducting research for new insights and innovative
solutions to health problems
Concentration Competencies Strengthened
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Identify & understand the historical context of
epidemiology, epidemiologic terminology, study
designs & methodology
Demonstrate communication skills key to public
health workforce participation and advocacy
Effectively manage public health programs and
projects
Demonstrate the principles of problem solving and
crisis management
Lessons Learned
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Challenges associated with Intellectual Property
Challenges in collaborative partnerships
between academic institutions
Research funding environment
Interactions with governmental agencies and
regulatory consultant groups
Thank You
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Dr. Nadine Rouphael – Emory University
The clinical research team at the Hope Clinic of the
Emory Vaccine Center.
Dr. Mark Prausnitz and the microneedle
development team at the Georgia Institute of
Technology
Dr. John Lednicky – University of Florida
References
Centers for Disease Control and Prevention. (2013). National early season flu
vaccination coverage, United States. Retrieved March 30, 2014 from
http://www.cdc.gov/flu/fluvaxview/nifs-estimates-nov2013.htm
Norman, J.J., Arya, J.M., McClain, M.A., Frew, P.M., Meltzer, M.I., & Prausnitz,
M.R. (2014). Microneedle patches: Usability and acceptability for selfvaccination against influenza. Vaccine, 32(16), 1856-1862.
Thompson, W.W. (2004). Influenza-associated hospitalizations in the United
States. Journal of the American Medical Association, 292(11), 13331340.
World Health Organization. (2009, April). Influenza (Seasonal). WHO Fact
Sheet, 211.
Zhu, Q., Zarnitsyn, V.G., Ye, L., Wen, Z, Gao, Y., Pan, L., Skountzou, I., et al.
(2009). Immunization by vaccine-coated microneedle arrays protects
against lethal influenza challenge. Proceedings of the National
Academy of Sciences of the United States of America, 106(19), 79687973.
Questions
http://drugdelivery.chbe.gatech.edu/Images/Image_gallery/Full/microneedle-patch2.jpg