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Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones.


ABSTRACT: 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.

SUBMITTER: Lima NS 

PROVIDER: S-EPMC9748393 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones.

Lima Noemia S NS   Musayev Maryam M   Johnston Timothy S TS   Wagner Danielle A DA   Henry Amy R AR   Wang Lingshu L   Yang Eun Sung ES   Zhang Yi Y   Birungi Kevina K   Black Walker P WP   O'Dell Sijy S   Schmidt Stephen D SD   Moon Damee D   Lorang Cynthia G CG   Zhao Bingchun B   Chen Man M   Boswell Kristin L KL   Roberts-Torres Jesmine J   Davis Rachel L RL   Peyton Lowrey L   Narpala Sandeep R SR   O'Connell Sarah S   Serebryannyy Leonid L   Wang Jennifer J   Schrager Alexander A   Talana Chloe Adrienna CA   Shimberg Geoffrey G   Leung Kwanyee K   Shi Wei W   Khashab Rawan R   Biber Asaf A   Zilberman Tal T   Rhein Joshua J   Vetter Sara S   Ahmed Afeefa A   Novik Laura L   Widge Alicia A   Gordon Ingelise I   Guech Mercy M   Teng I-Ting IT   Phung Emily E   Ruckwardt Tracy J TJ   Pegu Amarendra A   Misasi John J   Doria-Rose Nicole A NA   Gaudinski Martin M   Koup Richard A RA   Kwong Peter D PD   McDermott Adrian B AB   Amit Sharon S   Schacker Timothy W TW   Levy Itzchak I   Mascola John R JR   Sullivan Nancy J NJ   Schramm Chaim A CA   Douek Daniel C DC  

Nature communications 20221214 1


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  ...[more]

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