biostudies-literatureUnknown13(1)Lima NSNIH Intramural fundingAn important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. However, the basis for such cross-protection at the molecular level is incompletely understood. Here, we characterized the repertoire and epitope specificity of antibodies elicited by infection with the Beta, Gamma and WA1 ancestral variants and assessed their cross-reactivity to these and the more recent Delta and Omicron variants. We developed a method to obtain immunoglobulin sequences with concurrent rapid production and functional assessment of monoclonal antibodies from hundreds of single B cells sorted by flow cytometry. Infection with any variant elicited similar cross-binding antibody responses exhibiting a conserved hierarchy of epitope immunodominance. Furthermore, convergent V gene usage and similar public B cell clones were elicited regardless of infecting variant. These convergent responses despite antigenic variation may account for the continued efficacy of vaccines based on a single ancestral variant.Nature communications7733https://www.ebi.ac.uk/biostudies/studies/S-EPMC9748393biostudies-literaturePrimary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones.PMC9748393Yang ESHenry ARSchrager AShimberg GGordon IShi WMusayev MKhashab RWang JWang LAhmed AKwong PDTeng ITChen MO'Connell SSullivan NJRhein JWidge AMoon DWagner DALevy IMcDermott ABBirungi KJohnston TSRuckwardt TJTalana CANovik LRoberts-Torres JDouek DCBoswell KLNarpala SRDoria-Rose NAVetter SKoup RAGuech MO'Dell SBlack WPLorang CGSerebryannyy LZhao BSchmidt SDLima NSPegu ASchramm CASchacker TWDavis RLBiber APhung EMascola JRZhang YAmit SLeung KGaudinski MMisasi JPeyton LZilberman TfalsePrimary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones.An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. However, the basis for such cross-protection at the molecular level is incompletely understood. Here, we characterized the repertoire and epitope specificity of antibodies elicited by infection with the Beta, Gamma and WA1 ancestral variants and assessed their cross-reactivity to these and the more recent Delta and Omicron variants. We developed a method to obtain immunoglobulin sequences with concurrent rapid production and functional assessment of monoclonal antibodies from hundreds of single B cells sorted by flow cytometry. Infection with any variant elicited similar cross-binding antibody responses exhibiting a conserved hierarchy of epitope immunodominance. Furthermore, convergent V gene usage and similar public B cell clones were elicited regardless of infecting variant. These convergent responses despite antigenic variation may account for the continued efficacy of vaccines based on a single ancestral variant.2022-01-01T00:00:00Z2022 Dec2026-06-20T03:23:44.006Z2025-04-07T00:30:10.225ZS-EPMC97483933651746710.1038/s41467-022-35456-2