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.

KEY WORDS:

• human papillomavirus
• cervical cancer
• oropharyngeal cancer
• anogenital cancer
• non-melanoma skin cancer
• L2
• capsid display
• multimer
• toll-like receptor agonist
• adjuvant

Financial and competing interests disclosure

Research reported in this publication was supported by US Public Health Service grants (grants.nih.gov) from the National Cancer Institute of the National Institutes of Health under awards numbered R01CA118790 and P50CA09825 to RBSR. This work was also supported, in part, by a cooperative agreement from the US National Institutes of Health (National Institute of Allergy and Infectious Diseases) establishing the Epidemiology and Prevention Interdisciplinary Center for Sexually Transmitted Diseases (U19 AI113187). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Under a licensing agreement between Sanofi-Aventis and the Johns Hopkins University, R Roden is entitled to a share of royalty received by the University on sales of products. The value of these products could be impacted by the outcome of the study described in this article. Under a licensing agreement between PaxVax, the NIH, and the Johns Hopkins University, R Roden is entitled to a share of royalty received by the University on sales of the vaccine described in this article. R Roden is a co-founder of and has an equity ownership interest in Papivax LLC. Also, he owns Papivax Biotech Inc. stock options and is a member of Papivax Biotech Inc.’s Scientific Advisory Board. Under a licensing agreement between Papivax Biotech, Inc. and the Johns Hopkins University, the University is entitled to royalties on an invention described in this article. Under an option agreement between PathoVax LLC and the Johns Hopkins University and University of Vienna Medical School, R Roden and C Schellenbacher are entitled to distributions of payments associated with an invention described in this publication. R Roden and C Schellenbacher also own equity in PathoVax LLC and are members of its scientific advisory board. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. B Chackerian is a co-founder of and has an equity ownership interest in Agilvax, and is entitled to a share of royalties received by the University of New Mexico on intellectual property licensed to Agilvax. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.