title: Comparison of long-term 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: end-of-study analysis of a Phase III randomized trial.
abstract: The observer-blind, randomized, age-stratified, head-to-head study (NCT00423046) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18-45 y was completed. Five y after vaccination, in subjects from the Month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2.3-fold (36-45-y stratum) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16. For HPV-18, the fold differences were 12.1, 13.0 and 7.8, respectively. At Month 60, all (100%) subjects in HPV-16/18 vaccine group and the majority (95.7%-97.5%) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16. For HPV-18, the majority (98.1%-100%) of subjects in HPV-16/18 vaccine group were seropositive; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably (61.1%-76.9%) across the 3 age strata. In the total vaccinated cohort (received ≥1 dose regardless of baseline HPV serostatus and DNA status), geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Based on the 5-y data, piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine. Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses, comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection.
authors.affiliation: a Montefiore Medical Center and Albert Einstein College of Medicine; Obstetrics & Gynecology and Women's Health ; Bronx , NY USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Einstein
authors.forename: Peter
authors.initials: P
authors.lastname: Takacs
authors.forename: Archana
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Rhoda S
authors.initials: RS
authors.lastname: Sperling
authors.forename: Nahida
authors.initials: N
authors.lastname: Chakhtoura
authors.forename: Mark M
authors.initials: MM
authors.lastname: Blatter
authors.forename: Jacob
authors.initials: J
authors.lastname: Lalezari
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: David
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: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; 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 Al3+); AAHS, amorphous aluminum hydroxyphosphate sulfate; ANOVA, analysis of variance; AS04, Adjuvant System containing 3-O-desacyl-4’-monophosphoryl lipid A (MPL; ATP, according-to-protocol; CI, confidence interval; Cervarix®; ED50, effective dose producing 50% response; ELISA, enzyme-linked immunosorbent assay; GMT, geometric mean titer; Gardasil®; HPV, human papillomavirus; MSC, medically significant condition; NOAD, new onset autoimmune disease; NOCD, new onset chronic disease; PBNA, pseudovirion-based neutralization assay; SAE, serious adverse event; SP, seropositivity; TVC, total vaccinated cohort; antibodies; human papillomavirus; immunogenicity; models; nAb, neutralizing antibodies; neutralizing; safety; statistical