title: 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 years.
abstract: 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 (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck & 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 versus 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 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.
authors: Department of Obstetrics & Gynecology and Women's Health, Division of Gynecologic Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. meinstei@montefiore.org
authors: Mark H
authors: MH
authors: Einstein
authors: Mira
authors: M
authors: Baron
authors: Myron J
authors: MJ
authors: Levin
authors: Archana
authors: A
authors: Chatterjee
authors: Bradley
authors: B
authors: Fox
authors: Sofia
authors: S
authors: Scholar
authors: Jeffrey
authors: J
authors: Rosen
authors: Nahida
authors: N
authors: Chakhtoura
authors: Dorothée
authors: D
authors: Meric
authors: Francis J
authors: FJ
authors: Dessy
authors: Sanjoy K
authors: SK
authors: Datta
authors: Dominique
authors: D
authors: Descamps
authors: Gary
authors: G
authors: Dubin
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D052163:Human papillomavirus 6 / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18