Broad human and animal coronavirus neutralisation by SARS-CoV-2 S2-targeted vaccination

 Kevin W. Ng, Nikhil Faulkner, Katja Finsterbusch, Mary Wu, Ruth Harvey, Saira Hussain, Maria Greco, Yafei Liu, Svend Kjaer, Charles Swanton, Sonia Gandhi, Rupert Beale, Steve J. Gamblin, Peter Cherepanov, John McCauley, Rodney Daniels, Michael Howell,  

View ORCID ProfileHisashi Arase, Andeas Wack, David L.V. Bauer,  View ORCID ProfileGeorge Kassiotis

doi: https://doi.org/10.1101/2021.11.30.470568

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.11.30.470568v1.full.pdf

Abstract

Several common-cold coronaviruses (HCoVs) are endemic in humans and several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged during the current Coronavirus disease 2019 (COVID-19) pandemic. Whilst antibody cross-reactivity with the Spike glycoproteins (S) of diverse coronaviruses has been documented, it remains unclear whether such antibody responses, typically targeting the conserved S2 subunit, contribute to or mediate protection, when induced naturally or through vaccination. Using a mouse model, we show that prior HCoV-OC43 S immunity primes neutralising antibody responses to otherwise subimmunogenic SARS-CoV-2 S exposure and promotes S2-targeting antibody responses. Moreover, mouse vaccination with SARS-CoV-2 S2 elicits antibodies that neutralise diverse animal and human alphacoronaviruses and betacoronaviruses in vitro, and protects against SARS-CoV-2 challenge in vivo. Lastly, in mice with a history of SARS-CoV-2 Wuhan-based S vaccination, further S2 vaccination induces stronger and broader neutralising antibody response than booster Wuhan S vaccination, suggesting it may prevent repertoire focusing caused by repeated homologous vaccination. The data presented here establish the protective value of an S2-targeting vaccine and support the notion that S2 vaccination may better prepare the immune system to respond to the changing nature of the S1 subunit in SARS-CoV-2 variants of concern (VOCs), as well as to unpredictable, yet inevitable future coronavirus zoonoses.

Competing Interest Statement

The authors have declared no competing interest.

https://www.biorxiv.org/content/10.1101/2021.11.30.470568v1