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

被引:680
|
作者
Robbiani, Davide F. [1 ,9 ]
Gaebler, Christian [1 ]
Muecksch, Frauke [2 ]
Lorenzi, Julio C. C. [1 ]
Wang, Zijun [1 ]
Cho, Alice [1 ]
Agudelo, Marianna [3 ]
Barnes, Christopher O. [1 ]
Gazumyan, Anna [1 ]
Finkin, Shlomo [1 ]
Hagglof, Thomas [1 ]
Oliveira, Thiago Y. [1 ]
Viant, Charlotte [1 ]
Hurley, Arlene [4 ]
Hoffmann, Hans-Heinrich [5 ]
Millard, Katrina G. [1 ]
Kost, Rhonda G. [6 ]
Cipolla, Melissa [1 ]
Gordon, Kristie [1 ]
Bianchini, Filippo [1 ]
Chen, Spencer T. [1 ]
Ramos, Victor [1 ]
Patel, Roshni [1 ]
Dizon, Juan [1 ]
Shimeliovich, Irina [1 ]
Mendoza, Pilar [1 ]
Hartweger, Harald [1 ]
Nogueira, Lilian [1 ]
Pack, Maggi [1 ]
Horowitz, Jill [1 ]
Schmidt, Fabian [2 ]
Weisblum, Yiska [2 ]
Michailidis, Eleftherios [5 ]
Ashbrook, Alison W. [5 ]
Waltari, Eric [7 ]
Pak, John E. [7 ]
Huey-Tubman, Kathryn E. [3 ]
Koranda, Nicholas [3 ]
Hoffman, Pauline R. [3 ]
West, Anthony P., Jr. [3 ]
Rice, Charles M. [5 ]
Hatziioannou, Theodora [2 ]
Bjorkman, Pamela J. [3 ]
Bieniasz, Paul D. [2 ,8 ]
Caskey, Marina [1 ]
Nussenzweig, Michel C. [1 ,8 ]
机构
[1] Rockefeller Univ, Lab Mol Immunol, 1230 York Ave, New York, NY 10021 USA
[2] Rockefeller Univ, Lab Retrovirol, 1230 York Ave, New York, NY 10021 USA
[3] CALTECH, Div Biol & BioL Engn, Pasadena, CA 91125 USA
[4] Rockefeller Univ, Hosp Program Direct, 1230 York Ave, New York, NY 10021 USA
[5] Rockefeller Univ, Lab Virol & Infect Dis, 1230 York Ave, New York, NY 10021 USA
[6] Rockefeller Univ, Ctr Clin TransLat Sci, 1230 York Ave, New York, NY 10021 USA
[7] Chan Zuckerberg Biohub, San Francisco, CA USA
[8] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
[9] Univ Svizzera Italiana, Inst Res Biomed, Bellinzona, Switzerland
基金
美国国家卫生研究院;
关键词
NEUTRALIZING ANTIBODIES; SARS CORONAVIRUS; B-CELLS; BROAD;
D O I
10.1038/s41586-020-2456-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-2(1-5). 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 (IC(50)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. Although rare, antibodies against the receptor-binding domain of SARS-CoV-2 that showed potent antiviral activity were obtained from all tested convalescent individuals, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
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页码:437 / +
页数:20
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