RT Journal Article
SR Electronic
T1 Isolation and Characterization of Cross-Neutralizing Coronavirus Antibodies from COVID-19+ Subjects
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.23.436684
DO 10.1101/2021.03.23.436684
A1 Madeleine F. Jennewein
A1 Anna J. MacCamy
A1 Nicholas R. Akins
A1 Junli Feng
A1 Leah J. Homad
A1 Nicholas K. Hurlburt
A1 Emily Seydoux
A1 Yu-Hsin Wan
A1 Andrew B. Stuart
A1 Venkata Viswanadh Edara
A1 Katharine Floyd
A1 Abigail Vanderheiden
A1 John R. Mascola
A1 Nicole Doria-Rose
A1 Lingshu Wang
A1 Eun Sung Yang
A1 Helen Y. Chu
A1 Jonathan L. Torres
A1 Gabriel Ozorowski
A1 Andrew B. Ward
A1 Rachael E. Whaley
A1 Kristen W. Cohen
A1 Marie Pancera
A1 M. Juliana McElrath
A1 Janet A. Englund
A1 Andrés Finzi
A1 Mehul S. Suthar
A1 Andrew T. McGuire
A1 Leonidas Stamatatos
YR 2021
UL http://biorxiv.org/content/early/2021/03/24/2021.03.23.436684.abstract
AB 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 StatementL.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.