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

Cantoni, D. et al. (2022) Pseudotyped Bat Coronavirus RaTG13 is efficiently neutralised by convalescent sera from SARS-CoV-2 infected patients. Communications Biology, 5(1), 409. (doi: 10.1038/s42003-022-03325-9) (PMID:35505237) (PMCID:PMC9065041)

Abstract

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.

• Item Type: Articles
• Additional Information: D.B., J.N., N.T. and A.M. were funded by The Pirbright Institute’s BBSRC institute strategic programme grant (BBS/E/I/00007038) and by the MRC funded grant G2P-UK; A National Virology Consortium to address phenotypic consequences of SARS-CoV-2 genomic variation, (MR/W005611/1). D.C., M.M.N., A.N., A.C., P.S., J.C.O., H.B., N.J.T. and J.L.H. are members of Humoral Immune Correlates to COVID-19 (HICC) consortium, funded by the UKRI and NIHR; (COV0170 - HICC: Humoral Immune Correlates for COVID19, Grant Reference code: MC_PC_20016). J.L.H. & S.V. are funded by Innovate UK 72845 DIOSCoVax and CEPI. MMN and NJT are funded by Wellcome Trust/UK FCDO (GB-CHC210183)
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cantoni, Dr Diego
• Authors: Cantoni, D., Mayora-Neto, M., Thakur, N., Elrefaey, A. M. E., Newman, J., Vishwanath, S., Nadesalingam, A., Chan, A., Smith, P., Castillo-Olivares, J., Baxendale, H., Charleston, B., Heeney, J., Bailey, D., and Temperton, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Communications Biology
• Publisher: Nature Research
• ISSN: 2399-3642
• ISSN (Online): 2399-3642
• Copyright Holders: Copyright © The Author(s) 2022
• First Published: First published in Communications Biology 5(1): 409
• Publisher Policy: Reproduced under a Creative Commons licence