Developments in L2-based human papillomavirus (HPV) vaccines

Virus Res. 2017 Mar 2;231:166-175. doi: 10.1016/j.virusres.2016.11.020. Epub 2016 Nov 23.

Abstract

Infections with sexually transmitted high-risk Human Papillomavirus (hrHPV), of which there are at least 15 genotypes, are responsible for a tremendous disease burden by causing cervical, and subsets of other ano-genital and oro-pharyngeal carcinomas, together representing 5% of all cancer cases worldwide. HPV subunit vaccines consisting of virus-like particles (VLP) self-assembled from major capsid protein L1 plus adjuvant have been licensed. Prophylactic vaccinations with the 2-valent (HPV16/18), 4-valent (HPV6/11/16/18), or 9-valent (HPV6/11/16/18/31/33/45/52/58) vaccine induce high-titer neutralizing antibodies restricted to the vaccine types that cause up to 90% of cervical carcinomas, a subset of other ano-genital and oro-pharyngeal cancers and 90% of benign ano-genital warts (condylomata). The complexity of manufacturing multivalent L1-VLP vaccines limits the number of included VLP types and thus the vaccines' spectrum of protection, leaving a panel of oncogenic mucosal HPV unaddressed. In addition, current vaccines do not protect against cutaneous HPV types causing benign skin warts, or against beta-papillomavirus (betaPV) types implicated in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. In contrast with L1-VLP, the minor capsid protein L2 contains type-common epitopes that induce low-titer yet broadly cross-neutralizing antibodies to heterologous PV types and provide cross-protection in animal challenge models. Efforts to increase the low immunogenicity of L2 (poly)-peptides and thereby to develop broader-spectrum HPV vaccines are the focus of this review.

Keywords: Cervical cancer (CxCa); Cutaneous and anogenital warts (condylomata); HPV infection and disease; Human papillomavirus (HPV) vaccine; Minor capsid protein (L2); Squamous cell cancer (SCC).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Viral / biosynthesis*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / biosynthesis
  • Cancer Vaccines / immunology
  • Capsid Proteins / chemistry
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Cross Protection
  • Epitopes / chemistry
  • Epitopes / immunology
  • Female
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / prevention & control*
  • Head and Neck Neoplasms / virology
  • Humans
  • Immunity, Humoral / drug effects
  • Immunogenicity, Vaccine
  • Mice
  • Oncogene Proteins, Viral / chemistry
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae / drug effects
  • Papillomaviridae / growth & development
  • Papillomaviridae / immunology
  • Papillomaviridae / pathogenicity
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / biosynthesis
  • Papillomavirus Vaccines / immunology*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology
  • Vaccination*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / biosynthesis
  • Vaccines, Subunit / immunology
  • Vaccines, Virus-Like Particle

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cancer Vaccines
  • Capsid Proteins
  • Epitopes
  • L2 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Subunit
  • Vaccines, Virus-Like Particle