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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