Pseudotyped Bat Coronavirus RaTG13 is efficiently neutralised by convalescent sera from SARS-CoV-2 infected patients

Bat Coronavirus RaTG13, a sarbecovirus related to SARS-CoV-2, is more potently neutralized by antibodies from convalescent SARS-CoV-2-infected patients as well as vaccinated healthcare workers despite the spike proteins having high diversity within their receptor binding domains (RBD). RaTG13 is a close relative of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, sharing 96% sequence similarity at the genome-wide level. The spike receptor binding domain (RBD) of RaTG13 contains a number of amino acid substitutions when compared to SARS-CoV-2, likely impacting affinity for the ACE2 receptor. Antigenic differences between the viruses are less well understood, especially whether RaTG13 spike can be efficiently neutralised by antibodies generated from infection with, or vaccination against, SARS-CoV-2. Using RaTG13 and SARS-CoV-2 pseudotypes we compared neutralisation using convalescent sera from previously infected patients or vaccinated healthcare workers. Surprisingly, our results revealed that RaTG13 was more efficiently neutralised than SARS-CoV-2. In addition, neutralisation assays using spike mutants harbouring single and combinatorial amino acid substitutions within the RBD demonstrated that both spike proteins can tolerate multiple changes without dramatically reducing neutralisation. Moreover, introducing the 484 K mutation into RaTG13 resulted in increased neutralisation, in contrast to the same mutation in SARS-CoV-2 (E484K). This is despite E484K having a well-documented role in immune evasion in variants of concern (VOC) such as B.1.351 (Beta). These results indicate that the future spill-over of RaTG13 and/or related sarbecoviruses could be mitigated using current SARS-CoV-2-based vaccination strategies.

Automated summary

Bat coronavirus RaTG13, a close relative of SARS-CoV-2, can be more efficiently neutralized by antibodies from convalescent patients and vaccinated healthcare workers. RaTG13 and SARS-CoV-2 spike proteins can tolerate multiple amino acid substitutions within their receptor binding domains without dramatically reducing neutralization. Introducing the 484K mutation into RaTG13 enhances its neutralization, contrary to its role in immune evasion in SARS-CoV-2 variants of concern.