Viral vectored hepatitis C virus vaccines generate pan-genotypic T cell responses to conserved subdominant epitopes.
Adenovirus
Conserved sequence
Cross-reactive
Invariant chain
Universal HCV vaccine
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
06 07 2020
06 07 2020
Historique:
received:
08
12
2019
revised:
11
03
2020
accepted:
15
05
2020
pubmed:
14
6
2020
medline:
28
4
2021
entrez:
14
6
2020
Statut:
ppublish
Résumé
Viral genetic variability presents a major challenge to the development of a prophylactic hepatitis C virus (HCV) vaccine. A promising HCV vaccine using chimpanzee adenoviral vectors (ChAd) encoding a genotype (gt) 1b non-structural protein (ChAd-Gt1b-NS) generated high magnitude T cell responses. However, these T cells showed reduced cross-recognition of dominant epitope variants and the vaccine has recently been shown to be ineffective at preventing chronic HCV. To address the challenge of viral diversity, we developed ChAd vaccines encoding HCV genomic sequences that are conserved between all major HCV genotypes and adjuvanted by truncated shark invariant chain (sIi Age-matched female mice were immunised intramuscularly with ChAd (10 Conserved segment vaccines, ChAd-Gt1/3 and ChAd-Gt1-6, generated high-magnitude, broad, and functional CD4 We have demonstrated that genetically adjuvanted ChAd vectored HCV T cell vaccines encoding genetic sequences conserved between genotypes are immunogenic, activating T cells that target subdominant conserved HCV epitopes. These pre-clinical studies support the use of conserved segment HCV T cell vaccines in human clinical trials.
Sections du résumé
BACKGROUND
Viral genetic variability presents a major challenge to the development of a prophylactic hepatitis C virus (HCV) vaccine. A promising HCV vaccine using chimpanzee adenoviral vectors (ChAd) encoding a genotype (gt) 1b non-structural protein (ChAd-Gt1b-NS) generated high magnitude T cell responses. However, these T cells showed reduced cross-recognition of dominant epitope variants and the vaccine has recently been shown to be ineffective at preventing chronic HCV. To address the challenge of viral diversity, we developed ChAd vaccines encoding HCV genomic sequences that are conserved between all major HCV genotypes and adjuvanted by truncated shark invariant chain (sIi
METHODS
Age-matched female mice were immunised intramuscularly with ChAd (10
RESULTS
Conserved segment vaccines, ChAd-Gt1/3 and ChAd-Gt1-6, generated high-magnitude, broad, and functional CD4
CONCLUSIONS
We have demonstrated that genetically adjuvanted ChAd vectored HCV T cell vaccines encoding genetic sequences conserved between genotypes are immunogenic, activating T cells that target subdominant conserved HCV epitopes. These pre-clinical studies support the use of conserved segment HCV T cell vaccines in human clinical trials.
Identifiants
pubmed: 32532545
pii: S0264-410X(20)30687-3
doi: 10.1016/j.vaccine.2020.05.042
pii:
doi:
Substances chimiques
Epitopes
0
Epitopes, T-Lymphocyte
0
Viral Hepatitis Vaccines
0
Viral Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5036-5048Subventions
Organisme : Medical Research Council
ID : G0901723
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K010239/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N023668/1
Pays : United Kingdom
Organisme : MRF
ID : MRF_MRF-044-0001-RG-SWADL
Pays : United Kingdom
Informations de copyright
Copyright © 2020. Published by Elsevier Ltd.
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: ‘TD, AvD, SC, and EB are all contributors or inventors on patents for the conserved segment HCV T cell vaccines’.