Escape from neutralizing antibodies 1 by SARS-CoV-2 spike protein variants

Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C.C. Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D. Hillyer, Marina Caskey, Davide F. RobbianiCharles M. Rice, Michel C. Nussenzweig, Theodora Hatziioannou, Paul D. Bieniasz

Research output: Contribution to journalArticlepeer-review

879 Scopus citations

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.
Original languageEnglish (US)
JournaleLife
Volume9
DOIs
StatePublished - Oct 1 2020
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine
  • General Immunology and Microbiology
  • General Neuroscience

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