TY - JOUR T1 - 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. AU - Einstein,Mark H, AU - Levin,Myron J, AU - Chatterjee,Archana, AU - Chakhtoura,Nahida, AU - Takacs,Peter, AU - Catteau,Grégory, AU - Dessy,Francis J, AU - Moris,Philippe, AU - Lin,Lan, AU - Struyf,Frank, AU - Dubin,Gary, AU - ,, PY - 2014/12/9/entrez PY - 2014/12/9/pubmed PY - 2015/10/16/medline KW - 50 μg) adsorbed on aluminum salt (500 μg Al(OH)3) KW - ANOVA, analysis of variance KW - AS04, Adjuvant System containing 3-O-desacyl-4’-monophosphoryl lipid A (MPL KW - ATP, according-to-protocol KW - CI, confidence interval KW - CMI, cell-mediated immune KW - CVS, cervicovaginal secretion KW - Cervarix® KW - ED50, effective dose producing 50% response KW - ELISA, enzyme-linked immunosorbent assay KW - GM, geometric mean KW - GMR, geometric mean (titer) ratio KW - GMT, geometric mean titer KW - Gardasil® KW - HPA, Health Protection Agency KW - HPV, human papillomavirus KW - IgG, immunoglobulin G KW - MSC, medically significant condition KW - NOAD, new onset autoimmune disease KW - NOCD, new onset chronic disease KW - PBMC, peripheral blood mononuclear cells KW - PBNA, pseudovirion-based neutralization assay KW - SAE, serious adverse event KW - TVC, total vaccinated cohort KW - VLP, virus-like particle KW - human papillomavirus KW - immunogenicity KW - nAb(s), neutralizing antibody(ies) KW - safety SP - 3455 EP - 65 JF - Human vaccines & immunotherapeutics JO - Hum Vaccin Immunother VL - 10 IS - 12 N2 - 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. SN - 2164-554X UR - https://www.unboundmedicine.com/medline/citation/25483700/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_ L2 - https://www.tandfonline.com/doi/full/10.4161/hv.36117 DB - PRIME DP - Unbound Medicine ER -