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

• Published in: bioRxiv 2020-05
• Main Authors: Robbiani, Davide F, Gaebler, Christian, Muecksch, Frauke, Julio Cetrulo Lorenzi, Wang, Zijun, Cho, Alice, Agudelo, Marianna, Barnes, Christopher, Finkin, Shlomo, Hagglof, Thomas, Oliveira, Thiago, Viant, Charlotte, Hurley, Arlene, Millard, Katrina, Kost, Rhonda, Cipolla, Melissa, Gazumyan, Anna, Gordon, Kristie, Bianchini, Filippo, Chen, Spencer, Ramos, Victor, Patel, Roshni, Dizon, Juan, Shimeliovich, Irina, Mendoza, Pilar, Hartweger, Harald, Nogueira, Lilian, Pack, Maggi, Horowitz, Jill, Schmidt, Fabian, Weisblum, Yiska, Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Ashbrook, Alison, Waltari, Eric F, Pak, John, Huey-Tubman, Kathryn, Koranda, Nicholas, Hoffman, Pauline, West, Anthony, Rice, Charles, Hatziioannou, Theodora, Bjorkman, Pamela, Bieniasz, Paul, Caskey, Marina, Nussenzweig, Michel
• Format: Article
• Language: English
• Subjects: Antibody response; Antiviral activity; Coronaviruses; COVID-19; Epitopes; Immunoglobulins; Immunological memory; Lymphocytes B; Memory cells; Pandemics; Patent applications; Severe acute respiratory syndrome coronavirus 2; Spike protein; Vaccines
• DOI: 10.1101/2020.05.13.092619

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 neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning 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 (IC50s) 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. Competing Interest Statement In connection with this work The Rockefeller University has filed a provisional patent application on which D.F.R. and M.C.N are inventors. Footnotes * This version of the manuscript has been revised to include (i) analysis of 81 additional individuals, including hospitalized; (ii) characterization of 50 additional monoclonal antibodies; (iii) information on cross-reactivity to other coronaviruses; (iv) scripts for bioinformatic analysis of antibodies sequences; (v) structural information for 3 monoclonal antibodies; and (vi) neutralization data with real virus.