COVID-19 vaccination induces cross-neutralisation of sarbecoviruses related to SARS-CoV-2

West, G.E., Morse, R.B., Sievers, B.L. et al.  npj Vaccines 11, 125 (2026). https://doi.org/10.1038/s41541-026-01469-x

Abstract

Multi-dose vaccine schedules in a cohort of older individuals
with mixed infection histories induce strong humoral responses
against SARS-CoV-2 Wu-1 and early Omicron lineages.

The combined threats of future sarbecovirus zoonosis and continually emerging SARS-CoV-2 VOCs highlight the need to assess the breadth of existing SARS-CoV-2 vaccine-mediated protection. Here, we investigate a cohort of older individuals who received four COVID-19 vaccine doses, for potential cross-neutralisation against lentiviral particles bearing spikes from either Omicron VOCs or other sarbecoviruses. Despite recent fourth bivalent mRNA vaccine doses (encoding SARS-CoV-2 Wu-1 and Omicron spikes), neutralisation of Omicron lineage VOCs was reduced compared to Wu-1, consistent with an imprinted immune response.

Similarly, particles bearing either SARS-CoV-1 or a SARS-CoV-1-related bat sarbecovirus spike were neutralised less efficiently than Wu-1. Unexpectedly, however, we observed that particles with spikes from two animal SARS-CoV-2-related viruses, BANAL-20-52 from bats and a pangolin CoV, were significantly more sensitive to serum neutralising antibodies than SARS-CoV-2 Wu-1 itself. These surprising findings suggest that vaccine-mediated adaptive immunity may provide efficient cross-neutralisation and potential protection against certain animal sarbecoviruses.

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