Convergent antibody responses to SARS-CoV-2 in convalescent individuals
Authors: Jill Horowitz
Maggi Pack
Charles M Rice
Pauline R Hoffman
Alice Cho
Juan Dizon
Frauke Muecksch
Nicholas Koranda
Christian Gaebler
Spencer T Chen
Katrina G Millard
Julio C C Lorenzi
Fabian Schmidt
Eric Waltari
Arlene Hurley
Anna Gazumyan
Michel C Nussenzweig
Pilar Mendoza
Eleftherios Michailidis
Charlotte Viant
Victor Ramos
Filippo Bianchini
Kristie Gordon
Lilian Nogueira
Shlomo Finkin
Marina Caskey
Zijun Wang
Irina Shimeliovich
Alison W Ashbrook
Harald Hartweger
Rhonda G Kost
Hans-Heinrich Hoffmann
Roshni Patel
Paul D Bieniasz
Theodora Hatziioannou
Kathryn E Huey-Tubman
Thomas Hägglöf
Pamela J Bjorkman
Yiska Weisblum
John E Pak
Melissa Cipolla
Davide F Robbiani
Marianna Agudelo
Thiago Y Oliveira
Anthony P West Jr
Christopher O Barnes
Journal: Nature (2020)
Discipline: Multidisciplinary
Keywords: COVID-19; SARS-CoV-2; antibodies; plasma samples; neutralizing titres
Affiliations: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA. ., Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland. ., Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA., Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA., Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Hospital Program Direction, The Rockefeller University, New York, NY, USA., Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA., Center for Clinical Translational Science, The Rockefeller University, New York, NY, USA., Chan Zuckerberg Biohub, San Francisco, CA, USA., Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. ., Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA. ., Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. .

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. 

Retracted: No

PubPeer comments:
 Could you please tell me how to interpret the Circos plot in Figure 3? The way I understand the legend, the ribbons are supposed to link identical clonotypes found in the different donors, and the color code identifies relevant clonotypes. However, the red segment in patient Cov21 isn t linked to the red segment in patient Cov47. Similarly the orange segments in patients Cov21 and Cov72 are not linked, even though they are presented as examples of shared clonotypes in the table just below. Am I missing something here? Awesome piece of work, by the way. ,