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

Abstract

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 & 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 post-vaccination), 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%) versus 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.

Comparison of adaptive and innate immune responses induced by licensed vaccines for human papillomavirus

“…Differences in T-cell responses to the vaccine types (HPV-16 and HPV-18) and non-vaccine types (HPV-31 and HPV-45) between the vaccines have been observed, but it is unclear exactly how these differences impact underlying mechanisms of protection. 12,13 It is known that HPV VLP vaccination elicits a broad spectrum of ex vivo cytokine responses in whole blood samples, and analysis of cytokine production in L1 VLPstimulated peripheral blood mononuclear cells (PBMCs) following HPV-16 L1 vaccination showed that cytokine responses followed similar patters as neutralizing antibody responses. 14 However, the role of circulating cytokines in immunogenicity and long-term protection remains unknown.…”

High-Throughput Monitoring of Human Papillomavirus Type Distribution

“…The earliest outcome of HPV vaccination that can be monitored is changes in the HPV type-specific prevalences. The vaccines have some crossprotection against phylogenetically related HPV types not included in the vaccines (1,3,4), which might affect circulation of these related HPV types in vaccinated populations (5). It is also of interest to monitor whether the reduction of the vaccine types in the population may lead to increases in HPV prevalence of other HPV types ("type replacement"; ref.…”

Comparison between Urine and Cervical Samples for HPV DNA Detection and Typing in Young Women in Colombia

“…A large number of clinical trials have proven that these vaccines are safe, well tolerated, highly immunogenic, and effective in preventing persistent infections by HPV vaccine types as well as cervical intraepithelial lesions associated with them (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”