Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
- The Rockefeller University, United States
- New York Blood Center, United States
Abstract
Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files
Article and author information
Author details
Eleftherios Michailidis
Funding
National Institute of Allergy and Infectious Diseases (R37AI64003)
- Paul D Bieniasz
National Institute of Allergy and Infectious Diseases (R01AI078788)
- Theodora Hatziioannou
National Institute of Allergy and Infectious Diseases (P01AI138398-S1,2U19AI111825)
- Charles M Rice
- Michel C Nussenzweig
National Institute of Allergy and Infectious Diseases (R01AI091707-10S1)
- Charles M Rice
George Mason University (Fast Grant)
- Davide F Robbiani
- Charles M Rice
European ATAC Consortium (EC101003650)
- Davide F Robbiani
National Institutes of Health (UL1 TR001866)
- Christian Gaebler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Human plasma samples were obtained from volunteers at the New York Blood Center and Rockefeller University Hospital. Informed consent, and consent to publishers obtained. De-identified Plasma samples from the New York Blood Center were obtained under protocols approved by Institutional Review Boards at the New York Blood Center and authorized by donors under informed consent in accordance with federal, state and local laws and regulations which address protection of human subjects in research, including 45 CFR part 46. Plasma samples at the Rockefeller University were collected with Informed consent, and consent to publishers after review by the Rockefeller University IRB protocol number DRO-1006.
Copyright
© 2020, Weisblum et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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