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 Tdapwhen 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 65years 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.

Vaccine 29 (2011) 8459– 8465

Funded by Sanofi, non randomized study

Persistence of antibodies 3 years after booster vaccination of adults with combined acellular pertussis, diphtheria and tetanus

toxoids vaccineWayde 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.

Vaccine 29 (2011) 8483– 8486

GSK sponsored study done in USA

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.

Vaccine xxx (2011) xxx– xxx (article in press)

Canadian study, supported by Sanofi pasteur, canadian centre for vaccinology

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.

The Pediatric Infectious Disease Journal • Volume 30, Number 7, July 2011

Independent study done in CDC & WHO collaborating centre, Antwerp, Belgium. The university however receives research grant fro GSK

Kinetics of the Antibody Response to Tetanus-Diphtheria-Acellular Pertussis Vaccine in Women of Childbearing Age and

PostpartumWomenB. 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.

Clinical Infectious Diseases 2011;53(9):885–892

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

Impact of Maternal Postpartum Tetanus and Diphtheria Toxoids and Acellular Pertussis Immunization on Infant

Pertussis InfectionLuis 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.

Clinical Infectious Diseases Advance Access published November 10, 2011

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,

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 HPV-16/18 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.

www.thelancet.com/oncology Published online November 9, 2011 DOI:10.1016/S1470-2045(11)70287-X

GSK funded, Double blind RCT, large no of subjects, multicenteric, Pivotal study

Vaccine 29 (2011) 2011–2014

HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that maymediate cross-protectionTroy 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 cross-neutralizing antibodies are effectors of cross-protection observed for the HPV16/18 vaccine.

Study funded by Costa Rica Ministry of HealthThe authors have no conflict of interest. 2 authors are basic researchers of VLP HPV particles & gave it to both GSK & Merck

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 trialMatti 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

Human Vaccines 7:12, 1343-1358; December 2011; c 2011 Landes Bioscience

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% (HPV-16/18 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 enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodiesin 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.

The predicted impact of HPV vaccination on male infections and male HPV-related 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-and-male 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 vaccination-conferred 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 YearsResults From a Randomized StudySusanna 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**

(Pediatr Infect Dis J 2011;30: e49–e55)

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

Human Vaccines 7:12, 1374-1386; December 2011; c 2011 Landes Bioscience

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.

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 CanadaCatherine 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 controversyover mandatory immunization as was the case in the United States. Our findingssuggest an erosion of the persuasiveness of public good arguments around collectiveimmunization programs in the policy discourse.

J Public Health. 2011;101: 1850–1857. doi:10.2105/AJPH. 2011.300205)

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