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; Daniel C. Douek

doi:10.1038/s41467-022-35456-2

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

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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 language	English (US)
Article number	7733
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-35456-2
State	Published - 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.

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Lima, N. S., Musayev, M., Johnston, T. S., Wagner, D. A., Henry, A. R., Wang, L., Yang, E. S., Zhang, Y., Birungi, K., Black, W. P., O’Dell, S., Schmidt, S. D., Moon, D., Lorang, C. G., Zhao, B., Chen, M., Boswell, K. L., Roberts-Torres, J., Davis, R. L., ... Douek, D. C. (2022). Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones. Nature communications, 13(1), Article 7733. https://doi.org/10.1038/s41467-022-35456-2

Lima, NS, Musayev, M, Johnston, TS, Wagner, DA, Henry, AR, Wang, L, Yang, ES, Zhang, Y, Birungi, K, Black, WP, O’Dell, S, Schmidt, SD, Moon, D, Lorang, CG, Zhao, B, Chen, M, Boswell, KL, Roberts-Torres, J, Davis, RL, Peyton, L, Narpala, SR, O’Connell, S, Serebryannyy, L, Wang, J, Schrager, A, Talana, CA, Shimberg, G, Leung, K, Shi, W, Khashab, R, Biber, A, Zilberman, T, Rhein, J, Vetter, S, Ahmed, A, Novik, L, Widge, A, Gordon, I, Guech, M, Teng, IT, Phung, E, Ruckwardt, TJ, Pegu, A, Misasi, J, Doria-Rose, NA, Gaudinski, M, Koup, RA, Kwong, PD, McDermott, AB, Amit, S, Schacker, TW, Levy, I, Mascola, JR, Sullivan, NJ, Schramm, CA & Douek, DC 2022, 'Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones', Nature communications, vol. 13, no. 1, 7733. https://doi.org/10.1038/s41467-022-35456-2

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title = "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.",

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

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: {\textcopyright} 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-35456-2",

language = "English (US)",

volume = "13",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

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TY - JOUR

T1 - Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones

AU - Lima, Noemia S.

AU - Musayev, Maryam

AU - Johnston, Timothy S.

AU - Wagner, Danielle A.

AU - Henry, Amy R.

AU - Wang, Lingshu

AU - Yang, Eun Sung

AU - Zhang, Yi

AU - Birungi, Kevina

AU - Black, Walker P.

AU - O’Dell, Sijy

AU - Schmidt, Stephen D.

AU - Moon, Damee

AU - Lorang, Cynthia G.

AU - Zhao, Bingchun

AU - Chen, Man

AU - Boswell, Kristin L.

AU - Roberts-Torres, Jesmine

AU - Davis, Rachel L.

AU - Peyton, Lowrey

AU - Narpala, Sandeep R.

AU - O’Connell, Sarah

AU - Serebryannyy, Leonid

AU - Wang, Jennifer

AU - Schrager, Alexander

AU - Talana, Chloe Adrienna

AU - Shimberg, Geoffrey

AU - Leung, Kwanyee

AU - Shi, Wei

AU - Khashab, Rawan

AU - Biber, Asaf

AU - Zilberman, Tal

AU - Rhein, Joshua

AU - Vetter, Sara

AU - Ahmed, Afeefa

AU - Novik, Laura

AU - Widge, Alicia

AU - Gordon, Ingelise

AU - Guech, Mercy

AU - Teng, I. Ting

AU - Phung, Emily

AU - Ruckwardt, Tracy J.

AU - Pegu, Amarendra

AU - Misasi, John

AU - Doria-Rose, Nicole A.

AU - Gaudinski, Martin

AU - Koup, Richard A.

AU - Kwong, Peter D.

AU - McDermott, Adrian B.

AU - Amit, Sharon

AU - Schacker, Timothy W.

AU - Levy, Itzchak

AU - Mascola, John R.

AU - Sullivan, Nancy J.

AU - Schramm, Chaim A.

AU - Douek, Daniel C.

N1 - 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.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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ER -

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

Abstract

Bibliographical note

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