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

Noemia S. Lima, Maryam Musayev, Timothy S. Johnston, Danielle A. Wagner, Amy R. Henry, Lingshu Wang, Eun Sung Yang, Yi Zhang, Kevina Birungi, Walker P. Black, Sijy O’Dell, Stephen D. Schmidt, Damee Moon, Cynthia G. Lorang, Bingchun Zhao, Man Chen, Kristin L. Boswell, Jesmine Roberts-Torres, Rachel L. Davis, Lowrey Peyton, Sandeep R. Narpala, Sarah O’Connell, Leonid Serebryannyy, Jennifer Wang, Alexander Schrager, Chloe Adrienna Talana, Geoffrey Shimberg, Kwanyee Leung, Wei Shi, Rawan Khashab, Asaf Biber, Tal Zilberman, Joshua Rhein, Sara Vetter, Afeefa Ahmed, Laura Novik, Alicia Widge, Ingelise Gordon, Mercy Guech, I-Ting Teng, Emily Phung, Tracy J. Ruckwardt, Amarendra Pegu, John Misasi, Nicole A. Doria-Rose, Martin Gaudinski, Richard A. Koup, Peter D. Kwong, Adrian B. McDermott, Sharon Amit, Timothy W. Schacker, Itzchak Levy, John R. Mascola, Nancy J. Sullivan, Chaim A. Schramm () and Daniel C. Douek ()
Additional contact information
Noemia S. Lima: National Institutes of Health
Maryam Musayev: National Institutes of Health
Timothy S. Johnston: National Institutes of Health
Danielle A. Wagner: National Institutes of Health
Amy R. Henry: National Institutes of Health
Lingshu Wang: National Institutes of Health
Eun Sung Yang: National Institutes of Health
Yi Zhang: National Institutes of Health
Kevina Birungi: National Institutes of Health
Walker P. Black: National Institutes of Health
Sijy O’Dell: National Institutes of Health
Stephen D. Schmidt: National Institutes of Health
Damee Moon: National Institutes of Health
Cynthia G. Lorang: National Institutes of Health
Bingchun Zhao: National Institutes of Health
Man Chen: National Institutes of Health
Kristin L. Boswell: National Institutes of Health
Jesmine Roberts-Torres: National Institutes of Health
Rachel L. Davis: National Institutes of Health
Lowrey Peyton: National Institutes of Health
Sandeep R. Narpala: National Institutes of Health
Sarah O’Connell: National Institutes of Health
Leonid Serebryannyy: National Institutes of Health
Jennifer Wang: National Institutes of Health
Alexander Schrager: National Institutes of Health
Chloe Adrienna Talana: National Institutes of Health
Geoffrey Shimberg: National Institutes of Health
Kwanyee Leung: National Institutes of Health
Wei Shi: National Institutes of Health
Rawan Khashab: Sheba Medical Center
Asaf Biber: Sheba Medical Center
Tal Zilberman: Sheba Medical Center
Joshua Rhein: University of Minnesota Medical School
Sara Vetter: Minnesota Department of Health
Afeefa Ahmed: University of Minnesota Medical School
Laura Novik: National Institutes of Health
Alicia Widge: National Institutes of Health
Ingelise Gordon: National Institutes of Health
Mercy Guech: National Institutes of Health
I-Ting Teng: National Institutes of Health
Emily Phung: National Institutes of Health
Tracy J. Ruckwardt: National Institutes of Health
Amarendra Pegu: National Institutes of Health
John Misasi: National Institutes of Health
Nicole A. Doria-Rose: National Institutes of Health
Martin Gaudinski: National Institutes of Health
Richard A. Koup: National Institutes of Health
Peter D. Kwong: National Institutes of Health
Adrian B. McDermott: National Institutes of Health
Sharon Amit: Sheba Medical Center
Timothy W. Schacker: University of Minnesota Medical School
Itzchak Levy: Sheba Medical Center
John R. Mascola: National Institutes of Health
Nancy J. Sullivan: National Institutes of Health
Chaim A. Schramm: National Institutes of Health
Daniel C. Douek: National Institutes of Health

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35456-2

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