Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/61312 |
| _version_ | 1818024050308415488 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yiska Weisblum |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T03:54:03Z |
| format | Article |
| id | doaj.art-79b3d5db1a464b1183d621d965b32b35 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:54:03Z |
| publishDate | 2020-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-79b3d5db1a464b1183d621d965b32b352022-12-22T02:03:11ZengeLife Sciences Publications LtdeLife2050-084X2020-10-01910.7554/eLife.61312Escape from neutralizing antibodies by SARS-CoV-2 spike protein variantsYiska Weisblum0https://orcid.org/0000-0002-9249-1745Fabian Schmidt1https://orcid.org/0000-0001-7731-6685Fengwen Zhang2Justin DaSilva3Daniel Poston4Julio CC Lorenzi5Frauke Muecksch6https://orcid.org/0000-0002-0132-5101Magdalena Rutkowska7Hans-Heinrich Hoffmann8Eleftherios Michailidis9https://orcid.org/0000-0002-9907-4346Christian Gaebler10Marianna Agudelo11Alice Cho12Zijun Wang13Anna Gazumyan14Melissa Cipolla15Larry Luchsinger16https://orcid.org/0000-0002-0063-1764Christopher D Hillyer17Marina Caskey18Davide F Robbiani19Charles M Rice20https://orcid.org/0000-0003-3087-8079Michel C Nussenzweig21Theodora Hatziioannou22Paul D Bieniasz23https://orcid.org/0000-0002-2368-3719Laboratory of Retrovirology, The Rockefeller University, New York, United StatesLaboratory of Retrovirology, The Rockefeller University, New York, United StatesLaboratory of Retrovirology, The Rockefeller University, New York, United StatesLaboratory of Retrovirology, The Rockefeller University, New York, United StatesLaboratory of Retrovirology, The Rockefeller University, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United StatesLaboratory of Retrovirology, The Rockefeller University, New York, United StatesLaboratory of Retrovirology, The Rockefeller University, New York, United StatesLaboratory of Virology and Infectious Disease The Rockefeller University, New York, United StatesLaboratory of Virology and Infectious Disease The Rockefeller University, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United StatesLindsley F. Kimball Research Institute, New York Blood Center, New York, United StatesLindsley F. Kimball Research Institute, New York Blood Center, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United States; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, SwitzerlandLaboratory of Virology and Infectious Disease The Rockefeller University, New York, United StatesLaboratory of Molecular Immunology The Rockefeller University, New York, United States; Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesLaboratory of Retrovirology, The Rockefeller University, New York, United StatesLaboratory of Retrovirology, The Rockefeller University, New York, United States; Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesNeutralizing 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.https://elifesciences.org/articles/61312COVID19SARS-CoV-2VSVantibody |
| spellingShingle | 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 Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants eLife COVID19 SARS-CoV-2 VSV antibody |
| title | Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants |
| title_full | Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants |
| title_fullStr | Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants |
| title_full_unstemmed | Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants |
| title_short | Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants |
| title_sort | escape from neutralizing antibodies by sars cov 2 spike protein variants |
| topic | COVID19 SARS-CoV-2 VSV antibody |
| url | https://elifesciences.org/articles/61312 |
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