Abstract
Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)-reactive antibodies were detectable using a flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the immunoglobulin G (IgG) class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.
Highlights
Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans
To determine the degree of cross-reactivity between human coronaviruses (HCoVs) and SARS-CoV-2, we developed a flow cytometry– based assay for SARS-CoV-2–binding antibodies
The main target for such antibodies is the spike glycoprotein (S), which is proteolytically processed into the S1 and S2 subunits, mediating target cell attachment and entry, respectively
Summary
Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. This assay detected SARS-CoV-2 S–reactive IgM and IgA antibodies in COVID-19 convalescent sera
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