npj Viruses (Nov 2024)

Reduced cross-protective potential of Omicron compared to ancestral SARS-CoV-2 spike vaccines against potentially zoonotic coronaviruses

  • Tyler M. Renner,
  • Matthew Stuible,
  • Brian Cass,
  • Sylvie Perret,
  • Julie Guimond,
  • Simon Lord-Dufour,
  • Michael J. McCluskie,
  • Yves Durocher,
  • Bassel Akache

DOI
https://doi.org/10.1038/s44298-024-00067-9
Journal volume & issue
Vol. 2, no. 1
pp. 1 – 8

Abstract

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Abstract The COVID-19 pandemic has emphasised the importance of vaccines and preparedness against viral threats crossing species barriers. In response, a worldwide vaccination campaign targeting SARS-CoV-2 was implemented, which provides some cross-protective immunological memory to other coronavirus species with zoonotic potential. Following a vaccination regimen against SARS-CoV-2 spike in a preclinical mouse model, we were able to demonstrate the induction of neutralizing antibodies towards multiple human ACE2 (hACE2)-binding Sarbecovirus spikes. Importantly, compared to vaccines based on the SARS-CoV-2 Reference strain, vaccines based on Omicron spike sequences induced drastically less broadly cross-protective neutralizing antibodies against other hACE2-binding sarbecoviruses. This observation remained true whether the vaccination regimens were based on protein subunit or mRNA / LNP vaccines. Overall, while it may be necessary to update vaccine antigens to combat the evolving SARS-CoV-2 virus for enhanced protection from COVID-19, Reference-based vaccines may be a more valuable tool to protect against novel coronavirus zoonoses.