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Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.
Elife. 2020 10 28; 9E

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.

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Authors+Show Affiliations

Weisblum Y
Laboratory of Retrovirology, The Rockefeller University, New York, United States.
Schmidt F
Laboratory of Retrovirology, The Rockefeller University, New York, United States.
Zhang F
Laboratory of Retrovirology, The Rockefeller University, New York, United States.
DaSilva J
Laboratory of Retrovirology, The Rockefeller University, New York, United States.
Poston D
Laboratory of Retrovirology, The Rockefeller University, New York, United States.
Lorenzi JC
Laboratory of Molecular Immunology The Rockefeller University, New York, United States.
Muecksch F
Laboratory of Retrovirology, The Rockefeller University, New York, United States.
Rutkowska M
Laboratory of Retrovirology, The Rockefeller University, New York, United States.
Hoffmann HH
Laboratory of Virology and Infectious Disease The Rockefeller University, New York, United States.
Michailidis E
Laboratory of Virology and Infectious Disease The Rockefeller University, New York, United States.
Gaebler C
Laboratory of Molecular Immunology The Rockefeller University, New York, United States.
Agudelo M
Laboratory of Molecular Immunology The Rockefeller University, New York, United States.
Cho A
Laboratory of Molecular Immunology The Rockefeller University, New York, United States.
Wang Z
Laboratory of Molecular Immunology The Rockefeller University, New York, United States.
Gazumyan A
Laboratory of Molecular Immunology The Rockefeller University, New York, United States.
Cipolla M
Laboratory of Molecular Immunology The Rockefeller University, New York, United States.
Luchsinger L
Lindsley F. Kimball Research Institute, New York Blood Center, New York, United States.
Hillyer CD
Lindsley F. Kimball Research Institute, New York Blood Center, New York, United States.
Caskey M
Laboratory of Molecular Immunology The Rockefeller University, New York, United States.
Robbiani DF
Laboratory of Molecular Immunology The Rockefeller University, New York, United States. Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
Rice CM
Laboratory of Virology and Infectious Disease The Rockefeller University, New York, United States.
Nussenzweig MC
Laboratory of Molecular Immunology The Rockefeller University, New York, United States. Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
Hatziioannou T
Laboratory of Retrovirology, The Rockefeller University, New York, United States.
Bieniasz PD
Laboratory of Retrovirology, The Rockefeller University, New York, United States. Howard Hughes Medical Institute, The Rockefeller University, New York, United States.

MeSH

Angiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralBase SequenceCOVID-19COVID-19 VaccinesEpitopesGenes, ReporterHumansImmunization, PassiveMutationNeutralization TestsProtein DomainsProtein IsoformsReassortant VirusesReceptors, VirusSARS-CoV-2Selection, GeneticSpike Glycoprotein, CoronavirusVesiculovirusVirus ReplicationCOVID-19 Serotherapy

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33112236

Clinical Trial Links

RU Anti-SARS-CoV-2 (COVID-19) mAbs in Healthy Volunteers

Citation

Weisblum, Yiska, et al. "Escape From Neutralizing Antibodies By SARS-CoV-2 Spike Protein Variants." ELife, vol. 9, 2020.
Weisblum Y, Schmidt F, Zhang F, et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife. 2020;9.
Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C., Muecksch, F., Rutkowska, M., Hoffmann, H. H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., ... Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9. https://doi.org/10.7554/eLife.61312
Weisblum Y, et al. Escape From Neutralizing Antibodies By SARS-CoV-2 Spike Protein Variants. Elife. 2020 10 28;9 PubMed PMID: 33112236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. AU - Weisblum,Yiska, AU - Schmidt,Fabian, AU - Zhang,Fengwen, AU - DaSilva,Justin, AU - Poston,Daniel, AU - Lorenzi,Julio Cc, AU - Muecksch,Frauke, AU - Rutkowska,Magdalena, AU - Hoffmann,Hans-Heinrich, AU - Michailidis,Eleftherios, AU - Gaebler,Christian, AU - Agudelo,Marianna, AU - Cho,Alice, AU - Wang,Zijun, AU - Gazumyan,Anna, AU - Cipolla,Melissa, AU - Luchsinger,Larry, AU - Hillyer,Christopher D, AU - Caskey,Marina, AU - Robbiani,Davide F, AU - Rice,Charles M, AU - Nussenzweig,Michel C, AU - Hatziioannou,Theodora, AU - Bieniasz,Paul D, Y1 - 2020/10/28/ PY - 2020/07/22/received PY - 2020/10/27/accepted PY - 2020/10/29/pubmed PY - 2020/12/19/medline PY - 2020/10/28/entrez KW - COVID19 KW - SARS-CoV-2 KW - VSV KW - antibody KW - immunology KW - infectious disease KW - inflammation KW - microbiology KW - virus JF - eLife JO - Elife VL - 9 N2 - 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. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/33112236/Escape_from_neutralizing_antibodies_by_SARS_CoV_2_spike_protein_variants_ DB - PRIME DP - Unbound Medicine ER -