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Immunogenicity and Safety of Human Papillomavirus-16/18 AS04-adjuvanted Vaccine Coadministered With Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine and/or Meningococcal Conjugate Vaccine to Healthy Girls 11 to 18 Years of Age: Results From a Randomized Open Trial

Wheeler, Cosette M. PhD*; Harvey, Bryan M. MD; Pichichero, Michael E. MD; Simon, Michael W. MD§; Combs, Stephen P. MD; Blatter, Mark M. MD; Marshall, Gary S. MD**; Catteau, Grégory MSc††; Dobbelaere, Kurt MD††; Descamps, Dominique MD††; Dubin, Gary MD‡‡; Schuind, Anne MD‡‡

The Pediatric Infectious Disease Journal: December 2011 - Volume 30 - Issue 12 - p e225–e234
doi: 10.1097/INF.0b013e31822d28df
Online-Only: Original Studies

Background: A combined immunization strategy for administration of human papillomavirus (HPV) vaccine with other routine vaccines may lead to better compliance. Reactions and immunologic interference with concomitantly administered vaccines are unpredictable, necessitating clinical evaluation.

Methods: This was a randomized, open study conducted at 48 centers in the United States (NCT00369824). Healthy girls 11 to 18 years of age were randomized equally to 1 of 6 groups to receive 3 doses of HPV-16/18 AS04-adjuvanted vaccine administered at 0, 1, and 6 or 1, 2, and 7 months, with or without 1 dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) and/or 1 dose of meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MCV4) in different coadministration regimens (1283 girls vaccinated). Coadministered vaccines were injected at separate sites. Antibodies were measured for all vaccine components. Reactogenicity and safety were monitored.

Results: The prespecified criteria for noninferiority were met for all primary and secondary immunogenicity end points, demonstrating similar immunogenicity of Tdap and MCV4 when given alone or coadministered with the HPV vaccine. Immunogenicity of the HPV vaccine (in terms of seroconversion rates and geometric mean antibody titers to HPV antigens) was similar, regardless of whether it was given alone or coadministered with Tdap and/or MCV4. No differences were observed in the reactogenicity profile of the HPV vaccine administered alone or coadministered with either Tdap and/or MCV4 in different regimens.

Conclusions: Concomitant administration of HPV-16/18 AS04-adjuvanted vaccine with Tdap and/or MCV4 in different regimens did not interfere with the immune response to any of the vaccines and had an acceptable safety profile.

From the *Departments of Pathology and Obstetrics and Gynecology, University of New Mexico, Health Science Center, Albuquerque, NM; †Harvey Pediatrics, Jonesboro, AR; ‡Legacy Pediatrics, Rochester, NY; §Pediatric & Adolescent Medicine, Lexington, KY; ¶Gray Station Pediatrics, Gray, TN; ‖Pediatric Alliance, S.C., Pittsburgh, PA; **Department of Pediatrics, University of Louisville, Louisville, KY; ††GSK Biologicals, Wavre, Belgium; and ‡‡GSK Biologicals, King of Prussia, PA.

Accepted for publication July 11, 2011.

GlaxoSmithKline Biologicals was the funding source and was involved in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals also took in charge all costs associated with the development and the publishing of the present publication.

As part of the clinical study agreement, the sponsor (GSK) paid money to the institutions to conduct the study: Outside the scope of this submitted work, C.M.W. declares to have received travel/accommodations/meeting expenses from GSK for presenting study results; through the University of New Mexico, C.M.W. has received equipment and reagents for HPV genotyping from Roche Molecular Systems and funding for HPV vaccine studies from GSK and Merck and Co., Inc. (Roche Molecular Systems, GSK and Merck to the University of New Mexico). B.M.H. and M.W.S. declare to have no conflict of interest. M.E.P. declares to have received consulting fee or honorarium from GSK. S.P.C. declares to have received funds for conducting the study. M.M.B. has received payment toward Clinical research-GSK, Sanofi Pasteur, MSD, Wyeth, Novartis, MedImmune; Speakers bureau-GSK, Sanofi Pasteur; Advisory Boards-GSK, Sanofi Pasteur, MSD. G.S.M. has served as a principal investigator on studies funded by GlaxoSmithKline Biologicals. G.S.M. has also been an investigator on clinical trials funded by Merck, Novartis, and Sanofi Pasteur, and has received honoraria from these companies for lectures and service on advisory boards, G.C., K.D., D.D., G.D., A.S., all are currently employed by GSK Biologicals; K.D., D.D., G.D., and A.S. also hold stock ownership from the sponsoring company (GSK); G.D. also declares to have received royalty payments related to patents on a genital herpes vaccine candidate and has received reimbursement for travel and expenses for business-related activities from GSK.

Reprints: Cosette M. Wheeler, PhD, Departments of Pathology and Obstetrics and Gynecology, University of New Mexico, Health Science Center, Albuquerque, NM 87131. E-mail:

© 2011 Lippincott Williams & Wilkins, Inc.