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

Robbiani, Davide F.; Gaebler, Christian; Muecksch, Frauke; Lorenzi, Julio C. C.; Wang, Zijun; Cho, Alice; Agudelo, Marianna; Barnes, Christopher O.; Gazumyan, Anna; Finkin, Shlomo; Hägglöf, Thomas; Oliveira, Thiago Y.; Viant, Charlotte; Hurley, Arlene; Hoffmann, Hans-Heinrich; Millard, Katrina G.; Kost, Rhonda G.; Cipolla, Melissa; Gordon, Kristie; Bianchini, Filippo; Chen, Spencer T.; Ramos, Victor; Patel, Roshni; Dizon, Juan; Shimeliovich, Irina; Mendoza, Pilar; Hartweger, Harald; Nogueira, Lilian; Pack, Maggi; Horowitz, Jill; Schmidt, Fabian; Weisblum, Yiska; Michailidis, Eleftherios; Ashbrook, Alison W.; Waltari, Eric; Pak, John E.; Huey-Tubman, Kathryn E.; Koranda, Nicholas; Hoffman, Pauline R.; West, Anthony P.; Rice, Charles M.; Hatziioannou, Theodora; Bjorkman, Pamela J.; Bieniasz, Paul D.; Caskey, Marina; Nussenzweig, Michel C.

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(1–5). 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 titers: less than 1:50 in 33% and below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC(50)s) as low as single digit ng/mL. 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.