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Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

Robbiani, Davide F. and Gaebler, Christian and Muecksch, Frauke and Lorenzi, Julio C. C. and Wang, Zijun and Cho, Alice and Agudelo, Marianna and Barnes, Christopher O. and Gazumyan, Anna and Finkin, Shlomo and Hägglöf, Thomas and Oliveira, Thiago Y. and Viant, Charlotte and Hurley, Arlene and Hoffmann, Hans-Heinrich and Millard, Katrina G. and Kost, Rhonda G. and Gordon, Kristie and Cipolla, Melissa and Bianchini, Filippo and Chen, Spencer T. and Ramos, Victor and Patel, Roshni and Dizon, Juan and Shimeliovich, Irina and Mendoza, Pilar and Hartweger, Harald and Nogueira, Lilian and Pack, Maggi and Horowitz, Jill and Schmidt, Fabian and Weisblum, Yiska and Michailidis, Eleftherios and Ashbrook, Alison W. and Waltari, Eric and Pak, John E. and Huey-Tubman, Kathryn E. and Koranda, Nicholas and Hoffman, Pauline R. and West, Anthony P., Jr. and Rice, Charles M. and Hatziioannou, Theodora and Bjorkman, Pamela J. and Bieniasz, Paul D. and Caskey, Marina and Nussenzweig, Michel C. (2020) Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals. Nature . ISSN 0028-0836. PMCID PMC7263513. (In Press) https://resolver.caltech.edu/CaltechAUTHORS:20200518-082748284

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Abstract

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC₅₀ values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41586-020-2456-9DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263513PubMed CentralDiscussion Paper
https://doi.org/10.1101/2020.05.13.092619DOIDiscussion Paper
https://rdcu.be/b4566PublisherFree ReadCube access
ORCID:
AuthorORCID
Robbiani, Davide F.0000-0001-7379-3484
Huey-Tubman, Kathryn E.0000-0002-4683-8138
Rice, Charles M.0000-0003-3087-8079
Bjorkman, Pamela J.0000-0002-2277-3990
Nussenzweig, Michel C.0000-0003-0592-8564
Additional Information:© 2020 Springer Nature Limited. Received 03 May 2020. Accepted 12 June 2020. Published 18 June 2020. Online content: Any methods, additional references, Nature Research reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at https://doi.org/10.1038/s41586-020-2456-9 We thank all study participants who devoted time to our research; Drs. Barry Coller and Sarah Schlesinger, the Rockefeller University Hospital Clinical Research Support Office and nursing staff. Dr. Joseph L. DeRisi for facilitating interactions with the Chan Zuckerberg BioHub. All members of the M.C.N. laboratory for helpful discussions, Drs. Amelia Escolano, Gaëlle Breton and Bernardo Reis, and Maša Jankovic for laboratory support, and Dr. Jost Vielmetter and the Protein Expression Center in the Beckman Institute at Caltech. This work was supported by NIH grant P01-AI138398-S1 (M.C.N., C.M.R., P.J.B.) and 2U19AI111825 (M.C.N. and C.M.R).; the Caltech Merkin Institute for Translational Research and P50 AI150464 (P.J.B.), George Mason University Fast Grant (D.F.R. and P.J.B.) and the European ATAC consortium EC 101003650 (D.F.R.); 3 R01-AI091707-10S1 to C.M.R.; R37-AI64003 to P.D.B.; R01AI78788 to T.H.; The G. Harold and Leila Y. Mathers Charitable Foundation to C.M.R.. Electron microscopy was performed in the Caltech Beckman Institute Resource Center for Transmission Electron Microscpy (Drs. Songye Chen and Andrey Malyutin, Directors). C.G. was supported by the Robert S. Wennett Post-Doctoral Fellowship, in part by the National Center for Advancing Translational Sciences (National Institutes of Health Clinical and Translational Science Award program, grant UL1 TR001866), and by the Shapiro-Silverberg Fund for the Advancement of Translational Research. P.D.B. and M.C.N. are Howard Hughes Medical Institute Investigators. Author contributions: D.F.R., P.D.B., P.J.B., T.H., C.M.R. and M.C.N. conceived, designed and analyzed the experiments. D.F.R., M.C. and C.G. designed clinical protocols. F.M., J.C.C.L., Z.W., A.C., M.A., C.O.B., S.F., T.H., C.V., K.G., F.B., S.T.C., P.M., H.H., L.N., F.S., Y.W., H.-H.H., E.M., A.W.A., K.E.H.T., N.K. and P.R.H. carried out experiments. A.G. and M.C. produced antibodies. C.O.B., J.P. and E.W. produced SARS-CoV-2 proteins. A.H., R.K., J.H., K.G.M., C.G. and M.C. recruited participants and executed clinical protocols. R.P., J.D., M.P. and I.S. processed clinical samples. Data availability: Data are provided in SI Tables 1, 3, 4, 5 and 6; and in Figure 3 has associated raw sequencing data deposited at Github (https://github.com/stratust/igpipeline). This study also includes A Public Database of Memory and Naive B-Cell Receptor Sequences (https://datadryad.org/stash/dataset/doi:10.5061/dryad.35ks2), PDB datasets 6VYB and 6NB6 and Sequence Read Archive SRP010970. Code availability: Computer code to process the antibody sequences is available at GitHub (https://github.com/stratust/igpipeline).
Group:Richard N. Merkin Institute for Translational Research
Funders:
Funding AgencyGrant Number
NIHP01-AI138398-S1
NIH2U19AI111825
Caltech Merkin Institute for Translational ResearchUNSPECIFIED
NIHP50 AI150464
George Mason UniversityUNSPECIFIED
ATAC ConsortiumEC 101003650
NIH3 R01- AI091707-10S1
NIHR37-AI64003
NIHR01AI78788
G. Harold and Leila Y. Mathers Charitable FoundationUNSPECIFIED
Robert S. Wennett Postdoctoral FellowshipUNSPECIFIED
NIHUL1 TR001866
Shapiro-Silverberg FundUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
PubMed Central ID:PMC7263513
Record Number:CaltechAUTHORS:20200518-082748284
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200518-082748284
Official Citation:Robbiani, D.F., Gaebler, C., Muecksch, F. et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature (2020). https://doi.org/10.1038/s41586-020-2456-9
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103263
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:18 May 2020 15:44
Last Modified:22 Jun 2020 18:42

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