Abstract

The currently available nonavalent human papillomavirus (HPV) vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by the L1 virus-like particle (VLP) vaccine warrants further investigation into cross-protective L2 epitopes. The L2 proteins are yet to be fully characterized as to their precise placement in the virion. Adding to the difficulties in localizing L2, studies have suggested that L2 epitopes are not well exposed on the surface of the mature capsid prior to cellular engagement. Using a series of competition assays between previously mapped anti-L1 monoclonal antibodies (mAbs) (H16.V5, H16.U4 and H16.7E) and novel anti-L2 mAbs, we probed the capsid surface for the location of an L2 epitope (aa17–36). The previously characterized L1 epitopes together with our competition data is consistent with a proposed L2 epitope within the canyons of pentavalent capsomers.

Highlights

  • Human papillomaviruses (HPVs) are epitheliotropic viruses commonly thought to begin their infectious pathway through micro-abrasions in the skin or mucosae

  • The two HPV types responsible for the greatest number of cervical cancer cases are HPV16 and HPV18 and the research field has largely focused on these two high-risk types [2]

  • We report on the characterization of two novel anti-L2 monoclonal antibodies (mAbs) produced by immunizing mice with recombinant Adeno-associated virus like-particles concurrently displaying the HPV16 and HPV31 L2 aa17–36 epitopes [42]

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Summary

Introduction

Human papillomaviruses (HPVs) are epitheliotropic viruses commonly thought to begin their infectious pathway through micro-abrasions in the skin or mucosae. Over 170 different HPV types have been fully sequenced [1] and subsets of mucosal types are further defined as “high-risk” or “low-risk”. The low risk types are associated with benign skin warts of the hands, feet and genitals. The high-risk types are known to induce cervical cancer and are implicated in cancers of the mouth, oropharynx, vagina, anus and penis [2]. The two HPV types responsible for the greatest number of cervical cancer cases are HPV16 and HPV18 and the research field has largely focused on these two high-risk types [2]. The 8 kb double stranded DNA genome is encapsidated by a non-enveloped

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