Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials

Abstract

Background: The immunogenicity profile of the 9-valent HPV (9vHPV) vaccine was evaluated across five phase III clinical studies conducted in girls and boys 9-15 years of age and young women 16-26 years of age. The effect of baseline characteristics of subjects on vaccine-induced HPV antibody responses was assessed.

Methods: Immunogenicity data from 11,304 subjects who received ≥1 dose of 9vHPV vaccine in five Phase III studies were analyzed. Vaccine was administered as a 3-dose regimen. HPV antibody titers were assessed 1 month after dose 3 using a competitive Luminex immunoassay and summarized as geometric mean titers (GMTs). Covariates examined were age, gender, race, region of residence, and HPV serostatus and PCR status at day 1.

Results: GMTs to all 9 vaccine HPV types decreased with age at vaccination initiation, and were otherwise generally similar among the demographic subgroups defined by gender, race and region of residence. For all subgroups defined by race or region of residence, GMTs were higher in girls and boys than in young women. Vaccination of subjects who were seropositive at day 1 to a vaccine HPV type resulted in higher GMTs to that type, compared with those in subjects who were seronegative for that type at day 1.

Conclusions: 9vHPV vaccine immunogenicity was robust among subjects with differing baseline characteristics. It was generally comparable across subjects of different races and from different regions. Greater immunogenicity in girls and boys versus young women (the population used to establish 9vHPV vaccine efficacy in clinical studies) indicates that the anti-HPV responses generated by the vaccine in adolescents from all races or regions were sufficient to induce high-level protective efficacy. This immunogenicity profile supports a widespread 9vHPV vaccination program and early vaccination.

Keywords: 9v HPV vaccine; Clinical trial; Human papillomavirus; Immunogenicity; NCT00543543; NCT00943722; NCT00988884; NCT01073293; NCT01304498; V503-001; V503-002; V503-005; V503-007; V503-009/GDS01C.

Fig. 1

Plots of month 7 anti-HPV geometric mean titers (GMTs) responses in females to component human papillomavirus (HPV) vaccine types, by age at enrollment. GMTs with associated 95% confidence intervals are presented for the per-protocol immunogenicity population. cLIA, competitive Luminex-based immunoassay; mMU, milli-Merck units.