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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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 (US)
Article number7733
JournalNature communications
Issue number1
StatePublished - Dec 2022

Bibliographical note

Funding Information:
The authors would like to thank the members of the VRC 200 Study Team for their role in collecting samples that were used in this study: Lesia Drupolic, Lasonji Holman, Maria Burgos Florez, Charla Andrews, Britta Flach, Emily Coates, Obrimpong Amoa-Awua, Jennifer Cunningham, Pamela Costner, Floreliz Mendoza, William Whalen, Jamie Saunders, Laura Novik, Aba Eshun, Anita Arthur, Xiaolin Wang, Karen Parker, Abidemi Ola, Catina Evans, Jennifer Phipps, Pernell Williams, Justine Jones, Jackie Stephens, Jumoke Gbadebo, Preeti Apete, Renunda Hicks, LaShawn Requillman, Alison Beck, Seemal Awan, Richard Wu, Priya Kamath, Olga Trofymenko, Sarah Plummer, Nina Berkowitz, Olga Vasilenko, and Iris Pittman. The authors also thank Dr. Steven De Rosa (Fred Hutchinson Cancer Center) for providing a 28-color flow cytometry panel which we modified for our study and David Ambrozak for assistance with cell sorting. The authors thank Rodrigo Matus Nicodemus for his assistance in developing primers for RATP-Ig. Funding: This work was funded in part by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infection Disease, National Institutes of Health.

Funding Information:
Open Access funding provided by the National Institutes of Health (NIH).

Publisher Copyright:
© 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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