SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared with SARS-CoV-2 mRNA vaccinations
Elizabeth M. Anderson, Shuk Hang Li, Moses Awofolaju, Theresa Eilola, Eileen C. Goodwin, Marcus J. Bolton, Sigrid Gouma, Tomaz B. Manzoni, Philip Hicks, Rishi R. Goel, Mark M. Painter, Sokratis A. Apostolidis, Divij Mathew, Debora Dunbar, Danielle Fiore, Amanda Brock, JoEllen Weaver, John S. Millar, Stephanie DerOhannessian, Allison R. Greenplate, Ian Frank, Daniel J. Rader, E. John Wherry, Paul Bates, Scott E. Hensley
Abstract
It is important to determine if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and SARS-CoV-2 mRNA vaccinations elicit different types of antibodies. Here, we characterize the magnitude and specificity of SARS-CoV-2 spike-reactive antibodies from 10 acutely infected health care workers with no prior SARS-CoV-2 exposure history and 23 participants who received SARS-CoV-2 mRNA vaccines. We found that infection and primary mRNA vaccination elicit S1- and S2-reactive antibodies, while secondary vaccination boosts mostly S1 antibodies. Using absorption assays, we found that SARS-CoV-2 infections elicit a large proportion of original antigenic sin-like antibodies that bind efficiently to the spike of common seasonal human coronaviruses but poorly to the spike of SARS-CoV-2. In converse, vaccination modestly boosts antibodies reactive to the spike of common seasonal human coronaviruses, and these antibodies cross-react more efficiently to the spike of SARS-CoV-2. Our data indicate that SARS-CoV-2 infections and mRNA vaccinations elicit fundamentally different antibody responses.