IAPCOI dec-2011
TDAP
Recommendations for changes in and additional uses of Tdap:
● There is no minimum interval required or advised between receipt of a
tetanus toxoid– or diphtheria toxoid– containing vaccine and Tdap
when Tdap is otherwise indicated.
● A single dose of Tdap should be given to children 7 through 10 years of age
who have incomplete or unknown pertussis vaccine history. Additional
vaccines may be required on the basis of a catch-up schedule.
● A single dose of Tdap should be given to adults of any age (including those
aged 65 years or older) who have not received Tdap previously, who are
health care personnel, or who have or anticipate having close contact with
an infant younger than 12 months, such as grandparents and other
caregivers.
● A single dose of Tdap may be given in place of Td to any person aged 65
years or older who has not received Tdap previously.
Tolerability and antibody response in adolescents and adults
revaccinated with tetanus toxoid, reduced diphtheria toxoid, and acellular
pertussis vaccine adsorbed (Tdap) 4–5 years after a previous dose
Scott A. Halperina,∗ , Shelly McNeila , Joanne Langleya , Mark Blatter b , Marc Dionnec , Joanne Embreed ,
Roehl Johnsone, Thomas Latiolais f , William Meekisong, Francisco Noyah, Shelly Sendersi , Paul Zickler j ,
David R. Johnsonk
• Conclusion: A second dose of Tdap vaccine 5
years after the initial dose was well tolerated
and immunogenic in adolescents and adults.
Funded by Sanofi, non randomized study
Vaccine 29 (2011) 8459– 8465
Persistence of antibodies 3 years after booster vaccination of adults with
combined acellular pertussis, diphtheria and tetanus toxoids vaccine
Wayde Westona, Marc Messierb, Leonard R. Friedlanda, Xiangfeng Wua, Barbara Howea
• The duration of protection after vaccination with reduced antigen content
diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known.
• Long-term post-vaccination serological data will help to improve
understanding of the duration of humoral immunity and guide vaccination
policy for the timing of repeat dose administration.
• The persistence of antibodies to Tdap antigens was measured 3 years after
vaccination of adults 19–64 years of age with one of 2 Tdap vaccines
(Boostrix®, GlaxoSmithKline Biologicals; Tdap-B: or Adacel®, Sanofi
Pasteur; Tdap-A).
• In both groups, geometric mean concentrations for antibodies to
diphtheria, tetanus, and pertussis vaccine antigens were decreased at year
3 relative to levels observed 1 month and 1 year following vaccination, but
remained higher than pre-vaccination levels.
GSK sponsored study done in USA
Vaccine 29 (2011) 8483– 8486
Immune responses in adults to revaccination with a tetanus toxoid, reduced
diphtheria toxoid, and acellular pertussis vaccine
10 years after a previous dose ,
Scott A. Halperina,∗, David Scheifeleb, Gaston De Serres c, Francisco Noyad, William Meekisone, Q2 Paul Zickler f, Luc Larriveeg, Joanne
M. Langleya, Shelly A. McNeila, Simon Dobsonb, Emilia Jordanovh, Manoj Thakurh, Michael D. Deckerh, David R. Johnsoni
• Conclusion: A repeat dose of Tdap vaccine 10
years after the first dose was well tolerated
and immunogenic in adults.
Canadian study, supported by Sanofi pasteur, canadian centre for
vaccinology
Vaccine xxx (2011) xxx– xxx (article in press)
Protecting young infants
EFFECT OF A PREPREGNANCY BOOSTER DOSE ON MATERNAL ANTIBODY
TITERS IN YOUNG INFANTS
Elke Leuridan, MD, Niel Hens, MSc, PhD, Natasja Peeters, MB, Liene de Witte, MB,
Olivier Van der Meeren, MD, BSc,and Pierre Van Damme, MD, PhD
Abstract: To examine the influence of a pertussis booster
vaccination on the transfer of maternal antibodies, 24
nonpregnant women received a tetanus, diphtheria, acellular
pertussis booster vaccine between 2 consecutive pregnancies.
Blood was drawn from mothers and off-spring. Efficient
transplacental antibody transfer and significantly higher
antibody titers against 3 pertussis antigens were observed in
cord blood and in blood of 1-month-old infants born after a
maternal booster vaccination compared with results in their
siblings born before the booster administration.
Independent study done in CDC & WHO collaborating centre, Antwerp,
Belgium. The university however receives research grant fro GSK
The Pediatric Infectious Disease Journal • Volume 30, Number 7, July 2011
Kinetics of the Antibody Response to Tetanus-Diphtheria-Acellular
Pertussis Vaccine in Women of Childbearing Age and PostpartumWomen
B. A. Halperin, A. Morris, D. MacKinnon-Cameron, J. Mutch, J. M. Langley, S. A. McNeil, D. MacDougall, and S. A. Halperin
Conclusions. Although the antibody response to a dose
of Tdap in healthy nonpregnant women of
childbearing age and postpartum women occurs by
day 14 and is suggestive of an anamnestic immune
response, it may not be sufficiently rapid to protect
infants in the first weeks of life.
Canadian study done with educational grant from Sanofi pasteur, authors
have no conflict of interest, relevance of post partum Tdap vaccination to
prevent infant pertussis, random open design, serum IgG, IgA, breast milk
IgA measured
Clinical Infectious Diseases 2011;53(9):885–892
Impact of Maternal Postpartum Tetanus and Diphtheria Toxoids
and Acellular Pertussis Immunization on Infant Pertussis Infection
Luis A. Castagnini, C. Mary Healy, Marcia A. Rench, Susan H. Wootton, Flor M. Munoz, and Carol J. Baker
• Conclusions. Immunizing only postpartum mothers with
Tdap vaccine did not reduce pertussis illness in infants
#6 months of age. Efforts should be directed at
immunizing all household and key contacts of newborns
with Tdap, not just mothers.
Non industry funded study, done in USA, Good attempt to test the public
vaccine strategy. Pre & post intervention incidence compared in different time
periods. Poorly controlled health seeking practices and cocooning, variation in
laboratory confirmed cases only therefore missing out on some cases & low
incidence of pertussis are some limitations,
Clinical Infectious Diseases Advance Access published November 10, 2011
Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria
Toxoid and Acellular Pertussis Vaccine (Tdap) in Pregnant Women and
Persons Who Have or Anticipate Having Close Contact with an Infant Aged
<12 Months — Advisory Committee on Immunization Practices (ACIP), 2011
• ACIP reviewed published and unpublished data from VAERS, Sanofi
Pasteur (Adacel) and GlaxoSmithKline (Boostrix) pregnancy registries, and
small studies .
• ACIP concluded that administration of Tdap after 20 weeks’ gestation is
preferred to minimize the risk for any low-frequency adverse event and
the possibility that any spurious association might appear causative.
• IMPORTANT ISSUES
– Transplacental Maternal Antibodies: protection ?
– Interference with Infant Immune Response to Primary DTaP Vaccination
– Decision and Cost Effectiveness Analysis: cost effective
MMWR / October 21, 2011 / Vol. 60 / No. 41
HPV
Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine
against cervical infection and precancer caused by non-vaccine
oncogenic HPV types: 4-year end-of-study analysis of the randomised,
double-blind PATRICIA trial
Cosette M Wheeler, Xavier Castellsagué, Suzanne M Garland, Anne Szarewski, Jorma Paavonen, Paulo Naud, Jorge Salmerón, Song-Nan Chow, Dan
Apter, Henry Kitchener, Júlio C Teixeira, S Rachel Skinner, Unnop Jaisamrarn, Genara Limson, Barbara Romanowski, Fred Y Aoki, Tino F Schwarz, Willy
A J Poppe, F Xavier Bosch, Diane M Harper, Warner Huh, Karin Hardt, Toufi k Zahaf, Dominique Descamps, Frank Struyf, Gary Dubin, Matti Lehtinen, for
the HPV PATRICIA Study Group
Consistent vaccine efficacy against persistent infection and CIN2+ (with or without HPV-16/18 co-infection) was
seen across cohorts for HPV-33, HPV-31, HPV-45, and HPV-51. In the most conservative analysis of vaccine
efficacy against CIN2+, where all cases co-infected with HPV-16/18 were removed, vaccine efficacy was noted
for HPV-33 in all cohorts, and for HPV-31 in the ATP-E and TVC-naive. Vaccine efficacy against CIN2+
associated with the composite of 12 non-vaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68),
with or without HPV-16/18 co-infection, was 46·8% (95% CI 30·7–59·4) in the ATP-E, 56·2% (37·2–69·9) in the
TVC-naive, and 34·2% (20·4–45·8) in the TVC. Corresponding values for CIN3+ were 73·8% (48·3–87·9),
91·4% (65·0–99·0), and 47·5% (22·8–64·8)
Interpretation Data from the end-of-study analysis of PATRICIA show cross-protective efficacy of the HPV16/18 vaccine against four oncogenic non-vaccine HPV types—HPV-33, HPV-31, HPV-45, and HPV-51 in
different trial cohorts representing diverse groups of women.
GSK funded, Double blind RCT, large no of subjects, multicenteric, Pivotal study
www.thelancet.com/oncology Published online November 9, 2011 DOI:10.1016/S1470-2045(11)70287-X
HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may
mediate cross-protection
Troy J. Kempa, Allan Hildesheimb, Mahboobeh Safaeianb, Joseph G. Daunera, Yuanji Pana, Carolina
Porrasc, John T. Schiller d, Douglas R. Lowyd, Rolando Herreroc, Ligia A. Pintoa,
We observed that vaccination with CervarixTM induced cross-neutralizing
antibodies for HPV types for which evidence of vaccine efficacy has been
demonstrated (HPV31/45) but not for other types (HPV52/58). In addition,
HPV31/45 cross-neutralizing titers showed a significant increase with number of
doses (HPV31, p < 0.001; HPV45, p < 0.001) and correlated with HPV16/18
neutralizing titers, respectively. These findings raise the possibility that crossneutralizing antibodies are effectors of cross-protection observed for the
HPV16/18 vaccine.
Study funded by Costa Rica Ministry of Health
The authors have no conflict of interest. 2 authors are basic researchers of
VLP HPV particles & gave it to both GSK & Merck
Vaccine 29 (2011) 2011–2014
Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or
greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the
randomised, double-blind PATRICIA trial
Matti Lehtinen, Jorma Paavonen, Cosette M Wheeler, Unnop Jaisamrarn, Suzanne M Garland, Xavier Castellsagué, S Rachel Skinner, Dan Apter, Paulo
Naud, Jorge Salmerón, Song-Nan Chow, Henry Kitchener, Júlio C Teixeira, James Hedrick, Genara Limson, Anne Szarewski,
Barbara Romanowski, Fred Y Aoki, Tino F Schwarz, Willy A J Poppe, Newton S De Carvalho, Maria Julieta V Germar, Klaus Peters, Adrian Mindel,
Philippe De Sutter, F Xavier Bosch, Marie-Pierre David, Dominique Descamps, Frank Struyf, Gary Dubin, for the HPV PATRICIA Study Group*
PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+
and AIS irrespective of HPV DNA in the lesion. Population-based vaccination
that incorporates the HPV-16/18 vaccine and high coverage of early
adolescents might have the potential to substantially reduce the incidence of
cervical cancer.
www.thelancet.com/oncology Published online November 9, 2011 DOI:10.1016/S1470-2045(11)70286-8
Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18
vaccine and HPV-6/11/16/18 vaccine Follow-up from months 12–24 in a Phase III
randomized study of healthy women aged 18–45 y
In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18–26, 27–35, 36–45
y), were randomized (1:1) to receive the HPV-16/18 vaccine (CervarixR, GlaxoSmithKline Biologicals,
Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7
results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for
immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates
of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata,
100% (HPV-16/18 vaccine) and 97.5–100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0–100% (HPV16/18 vaccine) and 72.3–84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean
titers (GMTs) were 2.4–5.8- fold higher for HPV-16 and 7.7–9.4-fold higher for HPV-18 with the HPV-16/18
vaccine vs. the HPV-6/11/16/18 vaccine; HPV- 16 and HPV-18 GMTs were significantly higher with the
HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received
≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzymelinked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies
in cervicovaginal secretions (ELISA ) were not significantly different between vaccines. At Month 24, CD4+
T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell
response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16.
Both vaccines were generally well tolerated. . Although an immunological correlate of
protection has not been defined, differences in the magnitude of immune response
between vaccines may represent determinants of duration of protection.
Human Vaccines 7:12, 1343-1358; December 2011; c 2011 Landes Bioscience
The predicted impact of HPV vaccination on male infections and male HPVrelated cancers in Australia.
Smith MA, Lew JB, Walker RJ, Brotherton JM, Nickson C, Canfell K.
 National HPV Vaccination Program in 2007, with routine vaccination of 12-13
year old females and catch-up in females aged 13-26 years to 2009.
 to estimate the impact of the current female-only national vaccination program
on males, and then to estimate the incremental benefits to males from being
included in the program.
 The estimated 3-dose female coverage rates were 78% (range 70-80%) for
ongoing coverage in 12-13 year old girls; and from 74% (range 70-80%) in 14 year
olds, to 25% (range 15-35%) for women aged 26 years old in 2007.
 pre-vaccination HPV 16 prevalence in females and males aged 15-59 years was
3.2% and 3.1% respectively.
The current program in females is predicted to result in a 68% reduction in male
HPV 16 infections by 2050, leading to an estimated long term reduction of 14% in
rates of cancers of the head, neck and anogenital area. The estimated proportion
of the maximum possible vaccine-conferred benefit to males from a female-andmale program which will be achieved by female-only vaccination is 73% (range in
probabilistic sensitivity analysis: 53-78%).
 In conclusion, up to three-quarters of the maximum possible vaccinationconferred benefit to males due to reduced heterosexual transmission will be
achieved by the existing female-only program.
Vaccine. 2011 Nov 8;29(48):9112-22. Epub 2011 Mar 17.
Immunogenicity and Safety of Human Papillomavirus-16/18 AS04-Adjuvanted
Vaccine Administered According to an Alternative Dosing Schedule Compared With
the Standard Dosing Schedule in Healthy Women Aged 15 to 25 Years
Results From a Randomized Study
Susanna Esposito, MD,* Victoria Birlutiu, MD,† Pavol Jarcuska, PhD,‡ Antonio Perino, MD,§
Sorin Claudiu Man, PhD,¶ Radu Vladareanu, PhD, Dorothe´e Meric, MSc,** Kurt Dobbelaere, MD,**
Florence Thomas, DTM,** and Dominique Descamps, MD**
Conclusions: The third dose of the HPV-16/18 vaccine
can be administered any time between 6 and 12 months
after the first dose, with adequate immunogenicity and a
clinically acceptable safety profile
Study done in Italy, partial funding GSK, open design, random allocation,
serological study
(Pediatr Infect Dis J 2011;30: e49–e55)
Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted
vaccine administered as a 2-dose schedule compared with the
licensed 3-dose schedule: Results from a randomized study
The immunogenicity of the human papillomavirus (HPV)-16/18 AS 04-adjuvanted vaccine (CervarixR,
GlaxoSmithKline Biologicals) administered according to its licensed vaccination schedule (3-dose, 3D) and
formulation (20 μg of each HPV antigen; 20/20F) has previously been demonstrated. This partially-blind,
controlled, randomized trial (NCT00541970) evaluated 2-dose (2D) schedules using the licensed 20/20F
or an alternative formulation containing 40 μg of each antigen (40/40F), compared with the licensed 3D
schedule. Healthy females stratified by age (9–14, 15–19, 20–25 y) were randomized to receive 2 doses
of 20/20F at Months (M) 0,6 (n = 240), 40/40F at M0,6 (n = 241) or 40/40F at M0,2 (n = 240), or 3 doses of
20/20F at M0,1,6 (licensed schedule/formulation, n = 239). One month after the last dose, the 3D schedule
was not immunologically superior to 2D schedules except in the 40/40F M0,2 group for HPV-16 (lower limit
of 95% CI geometric mean antibody titer (GMT) ratio [2D/3D] <0.5). For both HPV-16 and HPV-18, the 2D
schedules in girls 9–14 y were immunologically non-inferior to the 3D schedule in women 15–25 y (the age
group in which efficacy has been demonstrated) (upper limit of 95% CI for GMT ratio [3D/2D] <2) one
month after the last dose. At Month 24, non-inferiority was maintained for the 2D M0,6 schedules in girls
9–14 y vs. the 3D schedule in women 15–25 y. All formulations had acceptable reactogenicity and safety
profiles.
These results indicate that the HPV-16/18 vaccine on a 2D M0,6
schedule is immunogenic and generally well tolerated in girls 9–14 y and
that the 2D schedule is likely adequate for younger females.
Human Vaccines 7:12, 1374-1386; December 2011; c 2011 Landes Bioscience
2012 Immunization Schedules for Children 0 Through 18 Years of Age
ACIP Meeting , October 25, 2011
2012 Schedule
– 7 Through 18 Years HPV (Footnote modification)
--Human papillomavirus vaccine (HPV). (Minimum age: 9 years)
–Quadrivalent HPV vaccine (Gardasil) or bivalent HPV vaccine (Cervarix)
is recommended for the prevention of cervical precancers and cancers in
females.
– Gardasil is recommended for prevention of cervical precancers and
cancers in females; anal cancer and genital warts in both females and
males.
–Routine vaccination for females and males is recommended as a 3-dose
series at 11 to 12 years of age. The series can be started beginning at 9
years of age.
–Administer the second dose 1 to 2 months after the first dose and the
third dose 6 months after the first dose (at least 24 weeks after the first
dose).
Another Look at theHumanPapillomavirus Vaccine Experience in Canada
Catherine L. Mah, MD, PhD, FRCPC, Raisa B. Deber, PhD, Astrid Guttmann, MDCM, MSc, FRCPC, Allison McGeer, MD, MSc, FRCPC,
and Murray Krahn, MD, MSc, FRCPC
Specifically, we show how a range of stakeholders framed HPV vaccination as a
personal—rather than a public—matter, despite the absence of a controversy
over mandatory immunization as was the case in the United States. Our findings
suggest an erosion of the persuasiveness of public good arguments around collective
immunization programs in the policy discourse.
J Public Health. 2011;101: 1850–1857. doi:10.2105/AJPH. 2011.300205)
Thank You & Merry Christmas