Preprint Article Version 1 This version is not peer-reviewed

Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-cell Vaccine

Edmund G.-T. Wee
,
Sarah Kempster
,
Deborah Ferguson
,
Joanna Hall
,
Claire Ham
,
Susan Morris
,
Alison Crook
,
Sarah C. Gilbert
,
Bette Korber
,
Neil Almond
,
Tomáš Hanke
*
Version 1 : Received: 31 July 2024 / Approved: 1 August 2024 / Online: 2 August 2024 (05:12:56 CEST)

How to cite: Wee, E. G.-T.; Kempster, S.; Ferguson, D.; Hall, J.; Ham, C.; Morris, S.; Crook, A.; Gilbert, S. C.; Korber, B.; Almond, N.; Hanke, T. Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-cell Vaccine. Preprints 2024, 2024080038. https://doi.org/10.20944/preprints202408.0038.v1 Wee, E. G.-T.; Kempster, S.; Ferguson, D.; Hall, J.; Ham, C.; Morris, S.; Crook, A.; Gilbert, S. C.; Korber, B.; Almond, N.; Hanke, T. Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-cell Vaccine. Preprints 2024, 2024080038. https://doi.org/10.20944/preprints202408.0038.v1

Abstract

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the key focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection in pre-clinical models and human trials. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses delivered by replication-deficient vector ChAdOx1. It focuses T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the beta-coronavirus family.

Keywords

COVID-19 vaccine; T cells; T cell vaccine; COVID-19 T cells; ChAdOx1; conserved region; Syrian hamster; challenge

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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