Cross-neutralizing protection of vaginal and oral mucosa from HPV challenge by vaccination in a mouse model

Author:

Sanders,Chelsea

Matthews,Rebecca

Esfahani, Sayyed Hamid Zarkesh

Khan,Nazneen

Patel,Nimit

Kalen,Joseph

Kirnbauer, Reinhard

Roden, Richard B

Difilippantonio,Simone

Pinto,Ligia

Shoemaker, Robert H

Marshall,Jason
Author Address

Laboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Laboratory of Viral Oncology (LVO), Department of Dermatology, Medical University of Vienna, Austria., Department of Pathology, Johns Hopkins University, Baltimore, MD, USA., Vaccine, Immunity, and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Chemopreventive Agent Development Research Group, Division of Cancer Prevention, NCI, Bethesda, MD, USA., Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. Electronic address: jason.marshall2@nih.gov.,

Abstract:

The species and tissue specificities of HPV (human papillomavirus) for human infection and disease complicates the process of prophylactic vaccine development in animal models. HPV pseudoviruses (PsV) that carry only a reporter plasmid have been utilized in vivo to demonstrate cell internalization in mouse mucosal epithelium. The current study sought to expand the application of this HPV PsV challenge model with both oral and vaginal inoculation and to demonstrate its utility for testing vaccine-mediated dual-site immune protection against several HPV PsV types. We observed that passive transfer of sera from mice vaccinated with the novel experimental HPV prophylactic vaccine RG1-VLPs (virus-like particles) conferred HPV16-neutralizing as well as cross-neutralizing Abs against HPV39 in naïve recipient mice. Moreover, active vaccination with RG1-VLPs also conferred protection to challenge with either HPV16 or HPV39 PsVs at both vaginal and oral sites of mucosal inoculation. These data support the use of the HPV PsV challenge model as suitable for testing against diverse HPV types at two sites of challenge (vaginal vault and oral cavity) associated with the origin of the most common HPV-associated cancers, cervical cancer and oropharyngeal cancer. Copyright © 2023. Published by Elsevier Ltd.

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