Explanations for the high potency of HPV prophylactic vaccines

John Schiller,Doug Lowy

doi:10.1016/j.vaccine.2017.12.079

Abstract

HPV L1 virus-like particle (VLP) vaccines administered in a prime/boost series of three injections over six months have demonstrated remarkable prophylactic efficacy in clinical trials and effectiveness in national immunization programs with high rates of coverage. There is mounting evidence that the vaccines have similar efficacy and effectiveness even when administered in a single dose. The unexpected potency of one dose of these VLP vaccines may largely be attributed to structural features of the particles, which lead to the efficient generation of long-lived antigen-specific antibody-producing cells and unique features of the virus life cycle that make the HPV virions highly susceptible to antibody-mediated inhibition of infection.

Highlights

The three commercial HPV prophylactic vaccines – Cervarix, Gardasil, and Gardasil-9 – are non-infectious subunit vaccines that contain virus-like particles (VLPs) of, respectively, HPV 16 and 18; HPV 6, 11, 16, and 18; and HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58
Post hoc analyses of three clinical trials, detailed in companion articles, have provided evidence that strong protection is induced in young women even after a single dose [6,7,8]
Surveillance studies strongly suggest that a single dose can reduce infection and neoplastic disease incidence in national immunization programs, as discussed in another companion article

Summary

Introduction

The three commercial HPV prophylactic vaccines – Cervarix, Gardasil, and Gardasil-9 – are non-infectious subunit vaccines that contain virus-like particles (VLPs) of, respectively, HPV 16 and 18; HPV 6, 11, 16, and 18; and HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58. Surveillance studies strongly suggest that a single dose can reduce infection and neoplastic disease incidence in national immunization programs, as discussed in another companion article,. We discuss why antibodies are likely to be the prime mediators of protection, why the VLPs are exceptionally strong inducers of durable antibody responses, and why the virus life cycle makes it especially responsive to antibody-mediated inhibition. Together, these explanations provide a biologically plausible rationale for why the HPV VLPs may be the first subunit vaccine to exhibit long term effectiveness after a single dose

Mechanisms of protection

Immunologic considerations

Findings

Virologic considerations