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 PeytonSandeep 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*, Daniel C. Douek*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number7733
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

Funding

FundersFunder number
National Institutes of Health
National Institute of Allergy and Infectious Diseases
Vaccine Research Center

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