Sustained Immunogenicity of 2-dose Human Papillomavirus 16/18 AS04-adjuvanted Vaccine Schedules in Girls Aged 9-14 Years: A Randomized Trial

Background. We previously reported the noninferiority 1 month after the last dose of 2-dose human papillomavirus 16/18 AS04-adjuvanted (AS04-HPV-16/18) vaccine schedules at months 0 and 6 (2D_M0,6) and months 0 and 12 (2D_M0,12) in girls aged 9-14 years compared with a 3-dose schedule at months 0, 1, and 6 (3D_M0,1,6) in women aged 15-25 years. Here, we report the results at study end (month 36 [M36]). Methods. Girls were randomized 1: 1 and received 2 vaccine doses either 6 months (2D_M0,6) or 12 months apart (2D_ M0,12); women received 3 doses at months 0, 1, and 6 (3D_M0,1,6). Endpoints included noninferiority of HPV-16/18 antibodies for 2D_ M0,6 versus 3D_M0,1,6; 2D_ M0,12 versus 3D_M0,1,6; and 2D_ M0,12 versus 2D_ M0,6; and assessment of neutralizing antibodies, T cells, B cells, and safety. Results. At M36, the 2D_ M0,6 and 2D_ M0,12 schedules remained noninferior to the 3D_M0,1,6 schedule in terms of sero-conversion rates and 3D/2D geometric mean titers for anti-HPV-16 and anti-HPV-18. All schedules elicited sustained immune responses up to M36. Conclusions. Both 2-dose schedules in young girls remained noninferior to the 3-dose schedule in women up to study conclusion at M36. The AS04-HPV-16/18 vaccine administered as a 2-dose schedule was immunogenic and well tolerated in young girls.