People who recovered from COVID-19 or received a vaccination show higher rates of cross-reactive immunity against closely related bat coronaviruses that pose potential spillover risks to humans, according to a joint study published in PLOS Biology by The Pirbright Institute and King’s College London (KCL). Scientists investigated how diverse bat sarbecoviruses interact with human and animal cell receptors, finding that viruses most capable of infecting multiple species share the closest evolutionary ties to SARS-CoV-2.
SARS-CoV-2 evolutionary group shows broad receptor usage
Researchers examined 15 representative bat coronavirus spike proteins using libraries of ACE2 receptors from 34 different species. Broad ACE2 usage, enabling entry into various host cells, appeared primarily in viruses within the same evolutionary group as SARS-CoV-2, including BANAL viruses discovered in Laos. Conversely, viruses from other evolutionary groups displayed more restricted receptor usage. For instance, a novel UK bat coronavirus designated RhGB07 showed specialized receptor constraints, and collaborators in Switzerland resolved its spike structure to aid the analysis.
“Our findings suggest that the bat coronaviruses currently considered most likely to spill over into humans are also most likely to be recognized by existing COVID-19 immunity,” said Dr Nazia Thakur, Pirbright postdoctoral scientist and lead author of the study. While spillover risk cannot be eliminated entirely, widespread exposure to SARS-CoV-2 may have elevated the barrier for related viruses to establish themselves in human populations, according to the research team.
COVID-19 antibodies neutralize related bat coronaviruses
To evaluate implications for human health, scientists analyzed blood samples from individuals who recovered from COVID-19. Antibodies from these donors successfully neutralized a range of closely related bat coronaviruses. The team also detected lower levels of neutralization against more distant bat sarbecoviruses, pointing to some degree of broader protection across the sub-group.
“These viruses showed the strongest antigenic similarity to SARS-CoV-2, meaning they were more readily recognized and neutralized by antibodies generated following COVID-19 infection,” said Katie Doores, professor of viral immunology at KCL. In contrast, more distantly related bat coronaviruses functioned as specialists, capable of utilizing ACE2 receptors from only a limited range of hosts.
Implications for Universal Vaccine Design
Further laboratory experiments at KCL and Pirbright identified several monoclonal antibodies capable of recognizing a diverse range of sarbecoviruses. A companion article published alongside the primary study mapped where these monoclonal antibodies bind, identifying conserved regions on the coronavirus spike protein. These conserved sites offer structural targets for the design of next-generation pan-sarbecovirus vaccines and therapeutics.
“One of the encouraging findings was evidence of cross-neutralization of even some of the more distantly related bat coronaviruses,” said Dr Dalan Bailey, head of Pirbright’s Viral Glycoproteins group. “This suggests that broadly protective, pan-sarbecovirus vaccines or therapeutics may be achievable.” The Biotechnology and Biological Sciences Research Council (UKRI), Wellcome, and the Medical Research Council (MRC) funded the research.
Frequently Asked Questions About Bat Coronaviruses and COVID-19 Immunity
Which bat coronaviruses showed the closest relationship to SARS-CoV-2?
Viruses displaying broad ACE2 receptor usage across multiple mammalian species, including the BANAL viruses discovered in Laos, belong to the same evolutionary group as SARS-CoV-2.
How did researchers test antibody effectiveness against these viruses?
Scientists examined blood samples taken from individuals who had recovered from COVID-19 to determine whether their antibodies could neutralize a panel of 15 representative bat coronavirus spike proteins.
What funding organizations supported this research?
The Biotechnology and Biological Sciences Research Council, Wellcome, and the Medical Research Council provided financial backing for the studies published in PLOS Biology.
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