Post-pandemic changes in population immunity have reduced the likelihood of emergence of zoonotic coronaviruses

Infections caused by endemic viruses, and the vaccines used to control them, often provide cross-protection against related viruses. This cross-protection has the potential to alter the transmission dynamics and likelihood of emergence of novel zoonotic viruses with pandemic potential. Here, we investigate how changes in population immunity after the COVID-19 pandemic have impacted the likelihood of emergence of a novel sarbecovirus, termed SARS-CoV-X. We show that sera from patients with different COVID-19 immunological histories possess cross-neutralising antibodies against the spike (S) protein of multiple zoonotic sarbecoviruses. Mathematical simulations using these viruses show a significant reduction in their likelihood of emergence in populations with current levels of SARS-CoV-2 natural and vaccine-derived immunity, with the outcome determined by the extent of cross-protection and the R0 of the novel virus. We also show that preventative vaccination programs against SARS-CoV-X using currently available COVID-19 vaccines can help resist emergence even in the presence of co-circulating SARS-CoV-2. However, it was possible for a theoretical vaccine with very high specificity to SARS-CoV-2 (i.e., one which elicits very low cross-protection against SARS-CoV-X) to increase the likelihood of SARS-CoV-X emergence, due to its effects on SARS-CoV-2 prevalence and, by extension, the levels of naturally-derived cross-protection in the human population. Overall, our findings show that SARS-CoV-2 circulation and COVID-19 vaccination have generated widespread population immunity against antigenically related sarbecoviruses, and this new immunological barrier is likely to be a strong determinant of the ability of novel sarbecoviruses to emerge in humans. One-Sentence SummaryFuture emergence of zoonotic coronaviruses is less likely due to post-pandemic shifts in population immunity.