TY - JOUR T1 - Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2- and 3-dose schedules in girls aged 9-14 years: Results to month 12 from a randomized trial. AU - Leung,Ting Fan, AU - Liu,Anthony Pak-Yin, AU - Lim,Fong Seng, AU - Thollot,Franck, AU - Oh,Helen May Lin, AU - Lee,Bee Wah, AU - Rombo,Lars, AU - Tan,Ngiap Chuan, AU - Rouzier,Roman, AU - Friel,Damien, AU - De Muynck,Benoit, AU - De Simoni,Stéphanie, AU - Suryakiran,Pemmaraju, AU - Hezareh,Marjan, AU - Folschweiller,Nicolas, AU - Thomas,Florence, AU - Struyf,Frank, PY - 2015/6/11/entrez PY - 2015/6/11/pubmed PY - 2016/5/10/medline KW - 2D, 2-dose KW - 3D, 3-dose KW - AAHS, aluminum hydroxyphosphate sulfate KW - ANOVA, analysis of variance KW - AS04, Adjuvant System containing 50 µg 3-O-desacyl-4 ′-monophosphoryl lipid A (MPL) adsorbed on aluminum salt (500 µg Al3+) KW - ATP-I, according-to-protocol immunogenicity cohort KW - CI, confidence interval KW - CMI, cell-mediated immunity KW - ED50, effective dose producing 50% response KW - ELISA, enzyme-linked immunosorbent assay KW - ELISPOT, enzyme-linked immunosorbent spot assay KW - EU, ELISA unit KW - GMR, geometric mean titer ratio KW - GMT, geometric mean antibody titer KW - HPV, human papillomavirus KW - HPV-16/18(2D), 2-dose schedule of the HPV-16/18 vaccine KW - HPV-6/11/16/18(2D), 2-dose schedule of the HPV-6/11/16/18 vaccine KW - HPV-6/11/16/18(3D), 3-dose schedule of the HPV-6/11/16/18 vaccine KW - IFNγ, interferon KW - IgG, immunoglobulin G KW - M, month(s) KW - PBMC, peripheral blood mononuclear cells KW - PBNA, pseudovirion-based neutralisation assay KW - SAE, serious adverse event KW - TVC, total vaccinated cohort KW - VLP, virus-like particle KW - administration schedule KW - female adolescents KW - human papillomavirus (HPV) vaccines KW - immunogenicity KW - pIMD, potential immune-mediated disease KW - safety KW - y, year(s) SP - 1689 EP - 702 JF - Human vaccines & immunotherapeutics JO - Hum Vaccin Immunother VL - 11 IS - 7 N2 - This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of 2 doses of the HPV-16/18 AS04-adjuvanted vaccine (HPV-16/18(2D)) vs. 2 or 3 doses of the HPV-6/11/16/18 vaccine (HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D)) in healthy girls aged 9-14 y. Girls were randomized (1:1:1) to receive HPV-16/18(2D) at months (M) 0,6 (N = 359), HPV-6/11/16/18(2D) at M0,6 (N = 358) or HPV-6/11/16/18(3D) at M0,2,6 (N = 358). The primary objective was non-inferiority/superiority of HPV-16/18 antibodies by ELISA for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) at M7 in the according-to-protocol immunogenicity cohort (ATP-I) and total vaccinated cohort, respectively. Secondary objectives included non-inferiority/superiority of HPV-16/18(2D) vs. HPV-6/11/16/18(3D) at M7, non-inferiority/superiority at M12, HPV-16/18 neutralizing antibodies, frequencies of T-cells/B-cells, reactogenicity and safety. Antibody responses at M7 for HPV-16/18(2D) were superior to those for HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) (lower limit of 95% confidence interval for geometric mean titer ratio (GMR) was >1): HPV-16/18(2D)/HPV-6/11/16/18(2D) GMRs were 1.69 [1.49-1.91] for anti-HPV-16 and 4.52 [3.97-5.13] for anti-HPV-18; HPV-16/18(2D)/HPV-6/11/16/18(3D) GMRs were 1.72 [1.54-1.93] for anti-HPV-16 and 3.22 [2.82-3.68] for anti-HPV-18; p = 0.0001 for all comparisons. Non-inferiority/superiority was also demonstrated at M12. Among initially seronegative girls in the ATP-I, neutralizing antibody titers were at least 1.8-fold higher for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) at M7 and M12. Frequencies of HPV-16/18-specific T-cells and B-cells were in similar ranges between groups. Reactogenicity and safety were in line with the known profile of each vaccine. In conclusion, superior HPV-16/18 antibody responses were elicited by 2 doses of the HPV-16/18 AS04-adjuvanted vaccine compared with 2 or 3 doses of the HPV-6/11/16/18 vaccine in girls (9-14 years). SN - 2164-554X UR - https://www.unboundmedicine.com/medline/citation/26062002/Comparative_immunogenicity_and_safety_of_human_papillomavirus__HPV__16/18_AS04_adjuvanted_vaccine_and_HPV_6/11/16/18_vaccine_administered_according_to_2__and_3_dose_schedules_in_girls_aged_9_14_years:_Results_to_month_12_from_a_randomized_trial_ L2 - https://www.tandfonline.com/doi/full/10.1080/21645515.2015.1050570 DB - PRIME DP - Unbound Medicine ER -