Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9-14 years: Results to month 36 from a randomized trial.
This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9-14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0, 6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4+ T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9-14 years.


CLINICAL TRIAL REGISTRATION
NCT0146235.
['Leung|Ting Fan|TF|', 'Liu|Anthony Pak-Yin|AP|', 'Lim|Fong Seng|FS|', 'Thollot|Franck|F|', 'Oh|Helen May Lin|HML|', 'Lee|Bee Wah|BW|', 'Rombo|Lars|L|', 'Tan|Ngiap Chuan|NC|', 'Rouzier|Roman|R|', 'De Simoni|Stéphanie|S|', 'Suryakiran|Pemmaraju|P|', 'Hezareh|Marjan|M|', 'Thomas|Florence|F|', 'Folschweiller|Nicolas|N|', 'Struyf|Frank|F|']
D000276:Adjuvants, Immunologic D000293:Adolescent D000536:Aluminum Hydroxide D000914:Antibodies, Viral D000917:Antibody Formation D001402:B-Lymphocytes D015496:CD4-Positive T-Lymphocytes D002648:Child D015331:Cohort Studies D005260:Female D052162:Human papillomavirus 16 D052161:Human papillomavirus 18 D006801:Humans D007111:Immunity, Cellular D007114:Immunization D007115:Immunization Schedule D000071497:Immunogenicity, Vaccine D009500:Neutralization Tests D027383:Papillomaviridae D030361:Papillomavirus Infections D053918:Papillomavirus Vaccines
Immunogenicity Safety Administration schedule Female adolescents Human papillomavirus vaccines