Convergent antibody responses to SARS-CoV-2 in convalescent individuals

Davide F. Robbiani (), Christian Gaebler, Frauke Muecksch, Julio C. C. Lorenzi, Zijun Wang, Alice Cho, Marianna Agudelo, Christopher O. Barnes, Anna Gazumyan, Shlomo Finkin, Thomas Hägglöf, Thiago Y. Oliveira, Charlotte Viant, Arlene Hurley, Hans-Heinrich Hoffmann, Katrina G. Millard, Rhonda G. Kost, Melissa Cipolla, Kristie Gordon, Filippo Bianchini, Spencer T. Chen, Victor Ramos, Roshni Patel, Juan Dizon, Irina Shimeliovich, Pilar Mendoza, Harald Hartweger, Lilian Nogueira, Maggi Pack, Jill Horowitz, Fabian Schmidt, Yiska Weisblum, Eleftherios Michailidis, Alison W. Ashbrook, Eric Waltari, John E. Pak, Kathryn E. Huey-Tubman, Nicholas Koranda, Pauline R. Hoffman, Anthony P. West, Charles M. Rice, Theodora Hatziioannou, Pamela J. Bjorkman (), Paul D. Bieniasz (), Marina Caskey () and Michel C. Nussenzweig ()
Additional contact information
Davide F. Robbiani: The Rockefeller University
Christian Gaebler: The Rockefeller University
Frauke Muecksch: The Rockefeller University
Julio C. C. Lorenzi: The Rockefeller University
Zijun Wang: The Rockefeller University
Alice Cho: The Rockefeller University
Marianna Agudelo: The Rockefeller University
Christopher O. Barnes: California Institute of Technology
Anna Gazumyan: The Rockefeller University
Shlomo Finkin: The Rockefeller University
Thomas Hägglöf: The Rockefeller University
Thiago Y. Oliveira: The Rockefeller University
Charlotte Viant: The Rockefeller University
Arlene Hurley: The Rockefeller University
Hans-Heinrich Hoffmann: The Rockefeller University
Katrina G. Millard: The Rockefeller University
Rhonda G. Kost: The Rockefeller University
Melissa Cipolla: The Rockefeller University
Kristie Gordon: The Rockefeller University
Filippo Bianchini: The Rockefeller University
Spencer T. Chen: The Rockefeller University
Victor Ramos: The Rockefeller University
Roshni Patel: The Rockefeller University
Juan Dizon: The Rockefeller University
Irina Shimeliovich: The Rockefeller University
Pilar Mendoza: The Rockefeller University
Harald Hartweger: The Rockefeller University
Lilian Nogueira: The Rockefeller University
Maggi Pack: The Rockefeller University
Jill Horowitz: The Rockefeller University
Fabian Schmidt: The Rockefeller University
Yiska Weisblum: The Rockefeller University
Eleftherios Michailidis: The Rockefeller University
Alison W. Ashbrook: The Rockefeller University
Eric Waltari: Chan Zuckerberg Biohub
John E. Pak: Chan Zuckerberg Biohub
Kathryn E. Huey-Tubman: California Institute of Technology
Nicholas Koranda: California Institute of Technology
Pauline R. Hoffman: California Institute of Technology
Anthony P. West: California Institute of Technology
Charles M. Rice: The Rockefeller University
Theodora Hatziioannou: The Rockefeller University
Pamela J. Bjorkman: California Institute of Technology
Paul D. Bieniasz: The Rockefeller University
Marina Caskey: The Rockefeller University
Michel C. Nussenzweig: The Rockefeller University

Nature, 2020, vol. 584, issue 7821, 437-442

Abstract: Abstract During the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has led to the infection of millions of people and has claimed hundreds of thousands of lives. The entry of the virus into cells depends on the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2. Although there is currently no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19-convalescent individuals. Plasma samples collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres; titres were less than 50 in 33% of samples, below 1,000 in 79% of samples and only 1% of samples had titres above 5,000. Antibody sequencing revealed the expansion of clones of RBD-specific memory B cells that expressed closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on the RBD neutralized the virus with half-maximal inhibitory concentrations (IC50 values) as low as 2 ng ml−1. In conclusion, most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

Date: 2020
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DOI: 10.1038/s41586-020-2456-9

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