Convergent antibody responses to SARS-CoV-2 in convalescent individuals.
Research paper by
Davide F DF Robbiani, Christian C Gaebler, Frauke F Muecksch, Julio C C JCC Lorenzi, Zijun Z Wang, Alice A Cho, Marianna M Agudelo, Christopher O CO Barnes, Anna A Gazumyan, Shlomo S Finkin, Thomas T Hägglöf, Thiago Y TY Oliveira, Charlotte C Viant, Arlene A Hurley, Hans-Heinrich HH Hoffmann, Katrina G KG Millard, Rhonda G RG Kost, Melissa M Cipolla, Kristie K Gordon, Filippo F Bianchini, Spencer T ST Chen, Victor V Ramos, Roshni R Patel, Juan J Dizon, Irina I Shimeliovich, Pilar P Mendoza, Harald H Hartweger, Lilian L Nogueira, Maggi M Pack, Jill J Horowitz, Fabian F Schmidt, Yiska Y Weisblum, Eleftherios E Michailidis, Alison W AW Ashbrook, Eric E Waltari, John E JE Pak, Kathryn E KE Huey-Tubman, Nicholas N Koranda, Pauline R PR Hoffman, Anthony P AP West, Charles M CM Rice, Theodora T Hatziioannou, Pamela J PJ Bjorkman, Paul D PD Bieniasz, Marina M Caskey, Michel C MC Nussenzweig
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 (IC 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.