eLife (Oct 2020)
Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
- Yiska Weisblum,
- Fabian Schmidt,
- Fengwen Zhang,
- Justin DaSilva,
- Daniel Poston,
- Julio CC 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 Robbiani,
- Charles M Rice,
- Michel C Nussenzweig,
- Theodora Hatziioannou,
- Paul D Bieniasz
Affiliations
- Yiska Weisblum
- ORCiD
- Laboratory of Retrovirology, The Rockefeller University, New York, United States
- Fabian Schmidt
- ORCiD
- Laboratory of Retrovirology, The Rockefeller University, New York, United States
- Fengwen Zhang
- Laboratory of Retrovirology, The Rockefeller University, New York, United States
- Justin DaSilva
- Laboratory of Retrovirology, The Rockefeller University, New York, United States
- Daniel Poston
- Laboratory of Retrovirology, The Rockefeller University, New York, United States
- Julio CC Lorenzi
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States
- Frauke Muecksch
- ORCiD
- Laboratory of Retrovirology, The Rockefeller University, New York, United States
- Magdalena Rutkowska
- Laboratory of Retrovirology, The Rockefeller University, New York, United States
- Hans-Heinrich Hoffmann
- Laboratory of Virology and Infectious Disease The Rockefeller University, New York, United States
- Eleftherios Michailidis
- ORCiD
- Laboratory of Virology and Infectious Disease The Rockefeller University, New York, United States
- Christian Gaebler
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States
- Marianna Agudelo
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States
- Alice Cho
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States
- Zijun Wang
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States
- Anna Gazumyan
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States
- Melissa Cipolla
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States
- Larry Luchsinger
- ORCiD
- Lindsley F. Kimball Research Institute, New York Blood Center, New York, United States
- Christopher D Hillyer
- Lindsley F. Kimball Research Institute, New York Blood Center, New York, United States
- Marina Caskey
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States
- Davide F Robbiani
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
- Charles M Rice
- ORCiD
- Laboratory of Virology and Infectious Disease The Rockefeller University, New York, United States
- Michel C Nussenzweig
- Laboratory of Molecular Immunology The Rockefeller University, New York, United States; Howard Hughes Medical Institute, The Rockefeller University, New York, United States
- Theodora Hatziioannou
- Laboratory of Retrovirology, The Rockefeller University, New York, United States
- Paul D Bieniasz
- ORCiD
- Laboratory of Retrovirology, The Rockefeller University, New York, United States; Howard Hughes Medical Institute, The Rockefeller University, New York, United States
- DOI
- https://doi.org/10.7554/eLife.61312
- Journal volume & issue
-
Vol. 9
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.
Keywords
