SUMMARY
SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterized 198 antibodies isolated from four COVID19+ subjects and identified 14 SARS-CoV-2 neutralizing antibodies. One targeted the NTD, one recognized an epitope in S2 and twelve bound the RBD. Three anti-RBD neutralizing antibodies cross-neutralized SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency rather than the antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. The anti-S2 antibody also neutralized SARS-CoV-1 and all four cross-neutralizing antibodies neutralized the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
Competing Interest Statement
L.S., M.P., and A.T.M. have filed a provisional patent application on the SARS-CoV-2 specific monoclonal antibodies from CV1, CV2 and PCV1. L.S., M.P., A.T.M., and A.F. have filed a provisional patent application on the mAbs from CV3. H.C. reports grants from Bill and Melinda Gates Foundation, and NIH during the conduct of the study; consulting with Merck and the Bill & Melinda Gates Foundation, grants from Sanofi Pasteur and Gates Ventures outside the submitted work, and non-financial support from Cepheid and Ellume.
