Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects.

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize 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 and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize 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 Interests: Declaration of interests L.S., M.P., and A.T.M. have filed a provisional patent application on the SARS-CoV-2-specific mAbs 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.Y.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.

(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)