Progress and prospects for L2-based human papillomavirus vaccines

Abstract

Human papillomavirus (HPV) is a worldwide public health problem, particularly in resource-limited countries. Fifteen high-risk genital HPV types are sexually transmitted and cause 5% of all cancers worldwide, primarily cervical, anogenital and oropharyngeal carcinomas. Skin HPV types are generally associated with benign disease, but a subset is linked to non-melanoma skin cancer. Licensed HPV vaccines based on virus-like particles (VLPs) derived from L1 major capsid antigen of key high risk HPVs are effective at preventing these infections but do not cover cutaneous types and are not therapeutic. Vaccines targeting L2 minor capsid antigen, some using capsid display, adjuvant and fusions with early HPV antigens or Toll-like receptor agonists, are in development to fill these gaps. Progress and challenges with L2-based vaccines are summarized.

Keywords: L2; adjuvant; anogenital cancer; capsid display; cervical cancer; human papillomavirus; multimer; non-melanoma skin cancer; oropharyngeal cancer; toll-like receptor agonist.

Figure 1

A RasMol-generated schematic of an MS2 VLP displaying a peptide representing HPV16 L2 (17-31). Red depicts the location of the N-terminus of the MS2 coat protein. L2 Peptides are displayed at the N-terminus of the viral coat protein (shown in red). In these recombinant VLPs, only 90 of the 180 coat proteins/VLP display the L2 peptide (shown in pink).