To compare HPV antibody responses in girls and boys aged 9-14 years who received 2 doses of 9-valent HPV (9vHPV) vaccine versus young women aged 16-26 years who received 3 doses.
Protocol V503-010 is an international, multi-centered, immunogenicity study of the 9vHPV vaccine. Subjects were enrolled in 5 cohorts: cohort 1: girls who received 2 doses of 9vHPV vaccine separated by a 6-month interval; cohort 2: boys who received 2 doses separated by a 6-month interval; cohort 3: girls and boys who received 2 doses separated by a 12-month interval; cohort 4 (control): young women who received 3 doses (at day 1, month 2, month 6); cohort 5 (exploratory): girls who received 3 doses (at day 1, month 2, month 6). HPV6/11/16/18/31/33/45/52/58 geometric mean titers (GMTs) and seroconversion rates were assessed at 1 month after the last dose using competitive Luminex immunoassay. The primary objectives of the study were to demonstrate non-inferior HPV antibody responses at 1 month after the last dose in cohort 1, cohort 2 and cohort 3 compared with cohort 4. The statistical criterion for non-inferiority required that the lower bound of the two-sided 95% confidence interval of GMT ratios (cohort 1/cohort 4, cohort 2/cohort 4, and cohort 3/cohort 4) be greater than 0.67 for each HPV type.
Marked elevations of GMTs were elicited in all five cohorts at 1 month after the last dose. GMTs for all 9 HPV types were non-inferior in girls and boys aged 9-14 years who received 2 doses (cohorts 1 , 2 and 3) compared with young women aged 16-26 years who received 3 doses (cohort 4). Therefore, the primary objectives of non-inferior immunogenicity of 2-dose vs. 3-dose regimens were met. Over 97.9% subjects seroconverted for all 9 vaccine HPV types. Exploratory analyses in girls aged 9-14 years showed that the 2-dose regimens (cohorts 1 and 3) resulted in lower GMTs than did the 3-dose regimen (cohort 5) for some of the HPV types.
Based on these non-inferiority results, and using the same approach as that previously accepted for licensure of 2-dose and 3-dose regimens of the quadrivalent HPV vaccine and the 3-dose regimen of the 9vHPV vaccine in girls and boys, efficacy findings in young women who received the 3-dose regimen of 9vHPV vaccine can be extended to girls and boys 9 to 14 years of age who received the 2-dose (0, 6) or (0, 12) regimen. No clinical significance can be assigned to the differences in GMTs between girls receiving 2 doses and girls receiving 3 doses since both groups had non-inferior immunogenicity compared with young women receiving 3 doses (the population and dose regimen used to establish 9vHPV vaccine efficacy).