Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18–45 years

摘要

Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines [HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck and Co., Inc.,] differ in terms of protection against oncogenic non-vaccine HPV types -31/45. The immune responses induced by the two vaccines against these two non-vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo postvaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed [HPV-010 (NCT00423046)]. Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA ) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0–16.7%) vs. the HPV-6/11/16/18 vaccine (0.0–5.0%) for HPV-45 with PBNA, but not ELISA . HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine {HPV-31 [geometric mean ratio (GMR) = 2.0; p = 0.0002] and HPV-45 [GMR = 2.6; p = 0.0092]}, as were the proportion of T-cell responders (HPV-31, p = 0.0009; HPV-45, p = 0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross-protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection.