Viral vectored hepatitis C virus vaccines generate pan-genotypic T cell responses to conserved subdominant epitopes.

Vaccine
Timothy DonnisonEleanor Barnes

Abstract

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 (sIitr). Age-matched female mice were immunised intramuscularly with ChAd (108 infectious units) encoding gt-1 and -3 (ChAd-Gt1/3) or gt-1 to -6 (ChAd-Gt1-6) conserved segments spanning the HCV proteome, or gt-1b (ChAd-Gt1b-NS control), with immunogenicity assessed 14-days post-vaccination. Conserved segment vaccines, ChAd-Gt1/3 and ChAd-Gt1-6, generated high-magnitude, broad, and functional CD4+ and CD8+ T cell responses. Compared to the ChAd-Gt1b-NS vaccine, these vaccines generated significantly greater responses against conserved non-gt-1 antigens, including conse...Continue Reading

Citations

Aug 13, 2020·International Journal of Molecular Sciences·Janine KemmingChristoph Neumann-Haefelin
Jan 30, 2021·Science·Nicholas M ProvinePaul Klenerman
Jun 3, 2021·Viruses·Johnathan D Guest, Brian G Pierce
Aug 11, 2021·Viruses·Christopher C PhelpsJonathan R Honegger
Aug 29, 2021·Current Opinion in Virology·Elahe Salimi AlizeiChristoph Neumann-Haefelin

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