Second-generation prophylactic HPV vaccines: successes and challenges

Abstract

The role of HPV as the causative factor in cervical cancer has led to the development of the HPV vaccines Gardasil and Cervarix. These vaccines effectively protect against two HPV types associated with 70% of cervical cancer cases. Despite this success, researchers continue to develop second-generation HPV vaccines to protect against more HPV types and allow increased uptake in developing countries. While a reformulated vaccine based on the current technology is currently in clinical trials, another strategy consists of targeting highly conserved epitopes in the minor capsid protein of HPV, L2. Vaccines targeting L2 induce broadly neutralizing antibodies, capable of blocking infection by a wide range of HPV types. Several vaccine designs have been developed to optimize the display of L2 epitopes to the immune system and to reduce the cost of manufacture and distribution. L2-based vaccines show considerable promise as a potential next-generation HPV vaccine.

Keywords::

• cervical cancer
• HPV
• L2
• vaccines
• virus-like particles

Financial & competing interests disclosure

The authors were supported by a grant from the US National Institutes of Health (NIH) (U19 AI084081) to the University of New Mexico Sexually Transmitted Infections Cooperative Research Center (STI-CRC). In addition, M Tyler is funded by a T32 training grant award by the US NIH to the University of New Mexico Infectious Disease and Immunity Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. B Chackerian and E Tumban are inventors of L2-VLP related patent applications licensed to Agilvax. Interactions with Agilvax are managed by the University of New Mexico in accordance with its conflict of interest policies. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• A subset of HPV types have been categorized as high-risk due to their involvement in the development in cervical cancer.

• Current HPV vaccines target HPV types 16 and 18; the two types responsible for 70% of cervical cancer cases.

• Current HPV vaccines largely do not protect against infection by other high-risk HPV types.

• A nonavalent vaccine targeting seven high-risk HPV types is in clinical trials.

• It is unlikely that vaccines targeting type-specific epitopes in the viral major capsid protein will be able to protect against all high-risk types.

• The minor capsid protein of HPV, L2, has been shown to contain epitopes that elicit cross-neutralizing antibodies when used as a recombinant protein vaccine.

• A number of approaches have been applied to increase the immunogenicity and cross-protective activity of L2-based vaccines.