title: Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: follow-up through Month 48 in a Phase III randomized study.
abstract: We previously reported higher anti-HPV-16 and -18 immune responses induced by HPV-16/18 vaccine compared with HPV-6/11/16/18 vaccine at Month 7 (one month after completion of full vaccination series) in women aged 18-45 y in an observer-blind study NCT00423046; the differences of immune response magnitudes were maintained up to Month 24. Here we report follow-up data through Month 48. At Month 48, in according-to-protocol cohort for immunogenicity (seronegative and DNA-negative for HPV type analyzed at baseline), geometric mean titers of serum neutralizing antibodies were 2.0- to 5.2-fold higher (HPV-16) and 8.6- to 12.8-fold higher (HPV-18) in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. The majority of women in both vaccine groups remained seropositive for HPV-16. The same trend was observed for HPV-18 in HPV-16/18 vaccine group; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably, particularly in the older age groups. In the total vaccinated cohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and -18 neutralizing antibody levels induced by HPV-16/18 vaccine were higher than those induced by HPV-6/11/16/18 vaccine. CD4+ T-cell response for HPV-16 and HPV-18 was higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Memory B-cell responses appeared similar between vaccine groups. Both vaccines were generally well tolerated. Overall, the higher immune response observed with the HPV-16/18 vaccine was maintained up to Month 48. A head-to-head study incorporating clinical endpoints would be required to confirm whether the observed differences in immune response between the vaccines influence the duration of protection they provided.
authors.affiliation: a Montefiore Medical Center; Albert Einstein College of Medicine; Department of Obstetrics & Gynecology and Women's Health ; Bronx , NY USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Einstein
authors.forename: Myron J
authors.initials: MJ
authors.lastname: Levin
authors.forename: Archana
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Nahida
authors.initials: N
authors.lastname: Chakhtoura
authors.forename: Peter
authors.initials: P
authors.lastname: Takacs
authors.forename: Grégory
authors.initials: G
authors.lastname: Catteau
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Dessy
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: Lan
authors.initials: L
authors.lastname: Lin
authors.forename: Frank
authors.initials: F
authors.lastname: Struyf
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D007156:Immunologic Memory; D008875:Middle Aged; D053918:Papillomavirus Vaccines / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: 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
keywords: 50 μg) adsorbed on aluminum salt (500 μg Al(OH)3); ANOVA, analysis of variance; AS04, Adjuvant System containing 3-O-desacyl-4’-monophosphoryl lipid A (MPL; ATP, according-to-protocol; CI, confidence interval; CMI, cell-mediated immune; CVS, cervicovaginal secretion; Cervarix®; ED50, effective dose producing 50% response; ELISA, enzyme-linked immunosorbent assay; GM, geometric mean; GMR, geometric mean (titer) ratio; GMT, geometric mean titer; Gardasil®; HPA, Health Protection Agency; HPV, human papillomavirus; IgG, immunoglobulin G; MSC, medically significant condition; NOAD, new onset autoimmune disease; NOCD, new onset chronic disease; PBMC, peripheral blood mononuclear cells; PBNA, pseudovirion-based neutralization assay; SAE, serious adverse event; TVC, total vaccinated cohort; VLP, virus-like particle; human papillomavirus; immunogenicity; nAb(s), neutralizing antibody(ies); safety