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

Author

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

Subjects
Science
Abstract

Vaccines against the WA1 SARS-CoV2 strain confer protection against other variants. However, the mechanisms underlying cross-protection are not fully understood. Here, the authors develop a method for rapid analysis of single B cells from patient samples and show that infection with a variant elicits convergent, public B cell responses to other variants.

Published
2022
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2. Convergent epitope specificities, V gene usage and public clones elicited by primary exposure to SARS-CoV-2 variants

Author

Noemia S, Lima, Maryam, Mukhamedova, 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, Jennifer, Wang, Alexander, Schrager, Chloe Adrienna, Talana, 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

Abstract

While humoral immune responses to infection or vaccination with ancestral SARS-CoV-2 have been well-characterized, responses elicited by infection with variants are less understood. Here we characterized the repertoire, epitope specificity, and cross-reactivity of antibodies elicited by Beta and Gamma variant infection compared to ancestral virus. We developed a high-throughput approach to obtain single-cell immunoglobulin sequences and isolate monoclonal antibodies for functional assessment. Spike-, RBD- and NTD-specific antibodies elicited by Beta- or Gamma-infection exhibited a remarkably similar hierarchy of epitope immunodominance for RBD and convergent V gene usage when compared to ancestral virus infection. Additionally, similar public B cell clones were elicited regardless of infecting variant. These convergent responses may account for the broad cross-reactivity and continued efficacy of vaccines based on a single ancestral variant.WA1, Beta and Gamma variants of SARS-CoV-2 all elicit antibody responses targeting similar RBD epitopes; public and cross-reactive clones are common.

Published
2022

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