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

康复者体内针对SARS-CoV-2的趋同抗体反应

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作者: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 Jr,Charles M Rice,Theodora Hatziioannou,Pamela J Bjorkman,Paul D Bieniasz,Marina Caskey,Michel C Nussenzweig

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.

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