A universal virus-like particle-based vaccine for human papillomavirus: Longevity of protection and role of endogenous and exogenous adjuvants

Antibodies targeting epitopes within the amino terminus of the minor capsid protein L2 of human papillomavirus (HPV) are broadly neutralizing against diverse HPV isolates. We have constructed bacteriophage virus-like particle (VLP)-based vaccines that display short L2 peptides and elicit high-titer and broadly protective antibody responses. Here, we further characterize two additional features of these VLP-based vaccines; the longevity of protection and the role of endogenous and exogenous adjuvants on the magnitude and characteristics of the antibody response. We show that vaccinated mice have long-lived antibody responses against L2, persisting over 18 months after vaccination. Vaccinated mice were strongly protected against infection by diverse HPV pseudoviruses over a year after immunization. We also show that exogenous and endogenous adjuvants (LPS and encapsidated single-stranded RNA) have minor effects on antibody titers. Immunization with VLPs containing encapsidated ssRNA predominantly shifts the response to a Th1, rather than a Th2-like response. Importantly, immunization with L2-VLPs (without endogenous and exogenous adjuvants) in the presence of alum hydroxide elicited a robust antibody response.