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 XXXX aged 9-14  years: Results to month 12 from a randomized trial.

@entity1 @entity1799 @entity855
UNASSIGNED: This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of 2 doses of the @entity1799 /18 AS04-adjuvanted vaccine ( @entity1799 /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 @entity1 aged 9-14 y. @entity1 were randomized (1:1:1) to receive @entity1799 /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 @entity1799 /18(2D) vs. HPV-6/11/16/18(2D) at M7 in the according-to-protocol immunogenicity cohort ( @entity855 -I) and total vaccinated cohort, respectively. Secondary objectives included non-inferiority/superiority of @entity1799 /18(2D) vs. HPV-6/11/16/18(3D) at M7, non-inferiority/superiority at M12, @entity1799 /18 neutralizing antibodies, frequencies of T-cells/B-cells, reactogenicity and safety. Antibody responses at M7 for @entity1799 /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): @entity1799 /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; @entity1799 /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 @entity1 in the @entity855 -I, neutralizing antibody titers were at least 1.8-fold higher for @entity1799 /18(2D) vs. HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) at M7 and M12. Frequencies of @entity1799 /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 @entity1799 /18 AS04-adjuvanted vaccine compared with 2 or 3 doses of the HPV-6/11/16/18 vaccine in @entity1 (9-14  years).
