SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines elicit higher levels of antibodies compared to natural SARS-CoV-2 infections in most individuals; however, the specificities of antibodies elicited by vaccination versus infection remain incompletely understood. Here, we characterized the magnitude and specificity of SARS-CoV-2 spike-reactive antibodies from 10 acutely infected health care workers and 23 participants who received mRNA-based SARS-CoV-2 vaccines. We found that infection and primary mRNA vaccination elicited S1 and S2-reactive antibodies, while secondary vaccination boosted mostly S1 antibodies. Using magnetic bead-based absorption assays, we found that SARS-CoV-2 infections elicited a large proportion of original antigenic sin-like antibodies that bound efficiently to common seasonal human coronaviruses but poorly to SARS-CoV-2. In converse, vaccination only modestly boosted antibodies reactive to common seasonal human coronaviruses and these antibodies bound efficiently to SARS-CoV-2. Our data indicate that SARS-CoV-2 mRNA vaccinations elicit fundamentally different antibody responses compared to SARS-CoV-2 infections. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/21264363v1_ufig1.gif" ALT="Figure 1"> View larger version (34K) org.highwire.dtl.DTLVardef@1352972org.highwire.dtl.DTLVardef@13419bcorg.highwire.dtl.DTLVardef@18595a5org.highwire.dtl.DTLVardef@1238eac_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LISARS-CoV-2 mRNA vaccines elicit higher levels of antibodies compared to SARS-CoV-2 infections C_LIO_LIThe first dose of an mRNA vaccine generates both S1 and S2 responses while the second dose boosts primarily S1-specific antibodies C_LIO_LISARS-CoV-2 infections, but not mRNA vaccinations, elicit high levels of antibodies that bind strongly to seasonal coronaviruses but weakly to SARS-CoV-2 C_LI