Abstract
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-21–5. 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 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.
