Explanations for the high potency of HPV prophylactic vaccines

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.

Keywords: HPV; Human papillomavirus; Prophylactic vaccine; Virus-like particle.

Fig. 1

Atomic model of HPV16 L1 VLP, reproduced from .

Fig. 2

B cell recognition of dense repetitive protein arrays promotes the induction of exceptionally potent and durable antibody responses. BCR = B cell receptors are shown in purple. The BCR-associated tyrosine kinases are depicted in blue. Protein antigens are grey.

Fig. 3

Cervicovaginal HPV infection in a mouse model. A disrupted cerviovaginal epithelium is depicted. “X” indicates the inability of virions to bind the apical surface of intact epithelium. HSPG = heparan sulfate proteoglycan. The L1 capsid structure is depicted in grey. The L2 minor capsid proteins, cleaved by furin protease after a HSPG binding-induced conformational change in the capsid, are shown in yellow.