Therapeutic Efficacy of a VSV-GP-based Human Papilloma Virus Vaccine in a Murine Cancer Model.
VSV-GP
cervical cancer
human papillomavirus (HPV)
therapeutic cancer vaccine
viral vector vaccine
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
01 07 2023
01 07 2023
Historique:
received:
22
11
2022
revised:
21
02
2023
accepted:
10
04
2023
medline:
5
6
2023
pubmed:
23
4
2023
entrez:
22
04
2023
Statut:
ppublish
Résumé
Human papilloma virus (HPV) infections are associated with almost all cervical cancers and to a lower extend also with anogenital or oropharyngeal cancers. HPV proteins expressed in HPV-associated tumors are attractive antigens for cancer vaccination strategies as self-tolerance, which is associated with most endogenous tumor-associated antigens, does not need to be overcome. In this study, we generated a live attenuated cancer vaccine based on the chimeric vesicular stomatitis virus VSV-GP, which has previously proven to be a potent vaccine vector and oncolytic virus. Genes at an earlier position in the genome more to the 3' end are expressed stronger compared to genes located further downstream. By inserting an HPV16-derived antigen cassette consisting of E2, E6 and E7 into VSV-GP either at first (HPVp1) or fifth (HPVp5) position in VSV-GP's genome we aimed to analyze the effect of vaccine antigen position and consequently expression level on viral fitness, immunogenicity, and anti-tumoral efficacy in a syngeneic mouse tumor model. HPVp1 expressed higher amounts of HPV antigens compared to HPVp5 in vitro but had a slightly delayed replication kinetic which overall translated into increased HPV-specific T cell responses upon vaccination of mice. Immunization with both vectors protected mice in prophylactic and in therapeutic TC-1 tumor models with HPVp1 being more effective in the prophylactic setting. Taken together, VSV-GP is a promising candidate as therapeutic HPV vaccine and first position of the vaccine antigen in a VSV-derived vector seems to be superior to fifth position.
Identifiants
pubmed: 37086948
pii: S0022-2836(23)00158-4
doi: 10.1016/j.jmb.2023.168096
pii:
doi:
Substances chimiques
Papillomavirus Vaccines
0
Vaccines, Attenuated
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
168096Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DvL and JK are inventors on patents related to VSV-GP. DvL serves as scientific advisors for Boehringer Ingelheim GmbH.