Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

Elaine C. Chen; Pavlo Gilchuk; Seth J. Zost; Naveenchandra Suryadevara; Emma S. Winkler; Carly R. Cabel; Elad Binshtein; Rita E. Chen; Rachel E. Sutton; Jessica Rodriguez; Samuel Day; Luke Myers; Andrew Trivette; Jazmean K. Williams; Edgar Davidson; Shuaizhi Li; Benjamin J. Doranz; Samuel K. Campos; Robert H. Carnahan; Curtis A. Thorne; Michael S. Diamond; James E. Crowe

doi:10.1016/j.celrep.2021.109604

Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

Elaine C. Chen, Pavlo Gilchuk, Seth J. Zost, Naveenchandra Suryadevara, Emma S. Winkler, Carly R. Cabel, Elad Binshtein, Rita E. Chen, Rachel E. Sutton, Jessica Rodriguez, Samuel Day, Luke Myers, Andrew Trivette, Jazmean K. Williams, Edgar Davidson, Shuaizhi Li, Benjamin J. Doranz, Samuel K. Campos, Robert H. Carnahan, Curtis A. ThorneMichael S. Diamond, James E. Crowe

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases, as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identify 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, angiotensin-converting enzyme 2 [ACE2]-blocking clone that protects in vivo) and others recognizing non-RBD epitopes that bind the S2 domain. Germline-revertant forms of some public clonotypes bind efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.

Original language	English
Article number	109604
Journal	Cell Reports
Volume	36
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2021.109604
State	Published - Aug 24 2021

Keywords

COVID-19
SARS-CoV
SARS-CoV-2
adaptive immunity
antibodies
coronavirus
human
monoclonal
public clonotypes
vaccines

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10.1016/j.celrep.2021.109604

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Chen, E. C., Gilchuk, P., Zost, S. J., Suryadevara, N., Winkler, E. S., Cabel, C. R., Binshtein, E., Chen, R. E., Sutton, R. E., Rodriguez, J., Day, S., Myers, L., Trivette, A., Williams, J. K., Davidson, E., Li, S., Doranz, B. J., Campos, S. K., Carnahan, R. H., ... Crowe, J. E. (2021). Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals. Cell Reports, 36(8), [109604]. https://doi.org/10.1016/j.celrep.2021.109604

@article{d4879ff37017408cb523065427741440,

title = "Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals",

abstract = "Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases, as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identify 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, angiotensin-converting enzyme 2 [ACE2]-blocking clone that protects in vivo) and others recognizing non-RBD epitopes that bind the S2 domain. Germline-revertant forms of some public clonotypes bind efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.",

keywords = "COVID-19, SARS-CoV, SARS-CoV-2, adaptive immunity, antibodies, coronavirus, human, monoclonal, public clonotypes, vaccines",

author = "Chen, {Elaine C.} and Pavlo Gilchuk and Zost, {Seth J.} and Naveenchandra Suryadevara and Winkler, {Emma S.} and Cabel, {Carly R.} and Elad Binshtein and Chen, {Rita E.} and Sutton, {Rachel E.} and Jessica Rodriguez and Samuel Day and Luke Myers and Andrew Trivette and Williams, {Jazmean K.} and Edgar Davidson and Shuaizhi Li and Doranz, {Benjamin J.} and Campos, {Samuel K.} and Carnahan, {Robert H.} and Thorne, {Curtis A.} and Diamond, {Michael S.} and Crowe, {James E.}",

note = "Funding Information: EM data collection was collected at the Center for Structural Biology Cryo-EM facility at Vanderbilt University. We thank Cinque Soto for technical advice on study of public clonotypes. We thank Rachel Nargi, Joseph Reidy, Erica Armstrong, and Christopher Gainza for support in antibody purifications. We also thank Berkeley Lights and Jonathan Didier for expert technical support, and STEMCELL Technologies and Aida Mayhew for supplying crucial B cell enrichment reagents. We thank Jem Uhrlaub, Brendan Larson, and Dr. Mike Worobey (University of Arizona) for preparation and sequencing of early-passage SARS-CoV-2 stocks. We thank Eun-Hyung Lee, Doan C. Nguyen, and Ignacio Sanz from Emory University for sharing the plasmablast survival medium that promotes antibody secretion. We thank the anonymous donors of the plasma samples for their consent that allowed the WHO International standard for anti-SARS-CoV-2 human immunoglobulin to be prepared; we express our gratitude to those who have coordinated the collection of the convalescent plasma: Malcom Semple (University of Liverpool, UK), Lance Turtle (University of Liverpool, UK), Peter Openshaw (Imperial College London, UK), and Kenneth Baillie (University of Edinburgh) on behalf of the ISARIC4C Investigators; and Heli Harvala Simmonds and David Roberts (National Health Service Blood and Transplant, UK). We also thank NIBSC Standards Production and Development staff for the formulation and distribution of materials. We thank Chris Selverian for assistance in epitope mapping and Mallorie Fouch for S2 binding studies. This work was supported by Defense Advanced Research Projects Agency (DARPA) grants HR0011-18-2-0001 and HR0011-18-3-0001; US NIH contracts 75N93019C00074, 75N93019C00062, and 75N93019C00073 (to B.J.D.); NIH grants AI150739, AI130591, R35 HL145242, AI157155, AI141707, AI12893, AI083203, AI149928, AI095202, AI083203, GM136853, DK103126, and UL1 TR001439; the Dolly Parton COVID-19 Research Fund at Vanderbilt; RII COVID-19 Seed Grant 002196 from University of Arizona; a grant from Fast Grants, Mercatus Center, George Mason University; and funding from AstraZeneca. E.C.C. was supported by NIH grant T32 AI138932, and E.S.W. was supported by NIH grant F30 AI152327. J.E.C. is a recipient of the 2019 Future Insight Prize from Merck KGaA, which supported this work with a grant. Conceptualization, E.C.C. and J.E.C.; investigation, E.C.C. P.G. S.J.Z. N.S. M.S.D. E.S.W. C.R.C. C.A.T. S.L. S.K.C. E.B. J.K.W. S.D. L.M. A.T. J.R. R.E.S. E.D. and R.E.C.; writing first draft: E.C.C. and J.E.C.; all authors edited the manuscript and approved the final submission; supervision, B.J.D. R.H.C. C.A.T. M.S.D. and J.E.C.; funding acquisition, M.S.D. and J.E.C. E.D. J.K.W. and B.J.D. are employees of Integral Molecular, and B.J.D. is a shareholder in that company. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and Carnival Corporation and is on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory has received funding support in sponsored research agreements from AstraZeneca, IDBiologics, and Takeda. Funding Information: E.D., J.K.W., and B.J.D. are employees of Integral Molecular, and B.J.D. is a shareholder in that company. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and Carnival Corporation and is on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory has received funding support in sponsored research agreements from AstraZeneca, IDBiologics, and Takeda. Funding Information: EM data collection was collected at the Center for Structural Biology Cryo-EM facility at Vanderbilt University. We thank Cinque Soto for technical advice on study of public clonotypes. We thank Rachel Nargi, Joseph Reidy, Erica Armstrong, and Christopher Gainza for support in antibody purifications. We also thank Berkeley Lights and Jonathan Didier for expert technical support, and STEMCELL Technologies and Aida Mayhew for supplying crucial B cell enrichment reagents. We thank Jem Uhrlaub, Brendan Larson, and Dr. Mike Worobey (University of Arizona) for preparation and sequencing of early-passage SARS-CoV-2 stocks. We thank Eun-Hyung Lee, Doan C. Nguyen, and Ignacio Sanz from Emory University for sharing the plasmablast survival medium that promotes antibody secretion. We thank the anonymous donors of the plasma samples for their consent that allowed the WHO International standard for anti-SARS-CoV-2 human immunoglobulin to be prepared; we express our gratitude to those who have coordinated the collection of the convalescent plasma: Malcom Semple (University of Liverpool, UK), Lance Turtle (University of Liverpool, UK), Peter Openshaw (Imperial College London, UK), and Kenneth Baillie (University of Edinburgh) on behalf of the ISARIC4C Investigators; and Heli Harvala Simmonds and David Roberts (National Health Service Blood and Transplant, UK). We also thank NIBSC Standards Production and Development staff for the formulation and distribution of materials. We thank Chris Selverian for assistance in epitope mapping and Mallorie Fouch for S2 binding studies. This work was supported by Defense Advanced Research Projects Agency (DARPA) grants HR0011-18-2-0001 and HR0011-18-3-0001 ; US NIH contracts 75N93019C00074 , 75N93019C00062 , and 75N93019C00073 (to B.J.D.); NIH grants AI150739 , AI130591 , R35 HL145242 , AI157155 , AI141707 , AI12893 , AI083203 , AI149928 , AI095202 , AI083203 , GM136853 , DK103126 , and UL1 TR001439 ; the Dolly Parton COVID-19 Research Fund at Vanderbilt ; RII COVID-19 Seed Grant 002196 from University of Arizona ; a grant from Fast Grants, Mercatus Center, George Mason University ; and funding from AstraZeneca . E.C.C. was supported by NIH grant T32 AI138932 , and E.S.W. was supported by NIH grant F30 AI152327 . J.E.C. is a recipient of the 2019 Future Insight Prize from Merck KGaA , which supported this work with a grant. Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = aug,

day = "24",

doi = "10.1016/j.celrep.2021.109604",

language = "English",

volume = "36",

journal = "Cell Reports",

issn = "2211-1247",

number = "8",

}

Chen, EC, Gilchuk, P, Zost, SJ, Suryadevara, N, Winkler, ES, Cabel, CR, Binshtein, E, Chen, RE, Sutton, RE, Rodriguez, J, Day, S, Myers, L, Trivette, A, Williams, JK, Davidson, E, Li, S, Doranz, BJ, Campos, SK, Carnahan, RH, Thorne, CA, Diamond, MS & Crowe, JE 2021, 'Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals', Cell Reports, vol. 36, no. 8, 109604. https://doi.org/10.1016/j.celrep.2021.109604

TY - JOUR

T1 - Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

AU - Chen, Elaine C.

AU - Gilchuk, Pavlo

AU - Zost, Seth J.

AU - Suryadevara, Naveenchandra

AU - Winkler, Emma S.

AU - Cabel, Carly R.

AU - Binshtein, Elad

AU - Chen, Rita E.

AU - Sutton, Rachel E.

AU - Rodriguez, Jessica

AU - Day, Samuel

AU - Myers, Luke

AU - Trivette, Andrew

AU - Williams, Jazmean K.

AU - Davidson, Edgar

AU - Li, Shuaizhi

AU - Doranz, Benjamin J.

AU - Campos, Samuel K.

AU - Carnahan, Robert H.

AU - Thorne, Curtis A.

AU - Diamond, Michael S.

AU - Crowe, James E.

N1 - Funding Information: EM data collection was collected at the Center for Structural Biology Cryo-EM facility at Vanderbilt University. We thank Cinque Soto for technical advice on study of public clonotypes. We thank Rachel Nargi, Joseph Reidy, Erica Armstrong, and Christopher Gainza for support in antibody purifications. We also thank Berkeley Lights and Jonathan Didier for expert technical support, and STEMCELL Technologies and Aida Mayhew for supplying crucial B cell enrichment reagents. We thank Jem Uhrlaub, Brendan Larson, and Dr. Mike Worobey (University of Arizona) for preparation and sequencing of early-passage SARS-CoV-2 stocks. We thank Eun-Hyung Lee, Doan C. Nguyen, and Ignacio Sanz from Emory University for sharing the plasmablast survival medium that promotes antibody secretion. We thank the anonymous donors of the plasma samples for their consent that allowed the WHO International standard for anti-SARS-CoV-2 human immunoglobulin to be prepared; we express our gratitude to those who have coordinated the collection of the convalescent plasma: Malcom Semple (University of Liverpool, UK), Lance Turtle (University of Liverpool, UK), Peter Openshaw (Imperial College London, UK), and Kenneth Baillie (University of Edinburgh) on behalf of the ISARIC4C Investigators; and Heli Harvala Simmonds and David Roberts (National Health Service Blood and Transplant, UK). We also thank NIBSC Standards Production and Development staff for the formulation and distribution of materials. We thank Chris Selverian for assistance in epitope mapping and Mallorie Fouch for S2 binding studies. This work was supported by Defense Advanced Research Projects Agency (DARPA) grants HR0011-18-2-0001 and HR0011-18-3-0001; US NIH contracts 75N93019C00074, 75N93019C00062, and 75N93019C00073 (to B.J.D.); NIH grants AI150739, AI130591, R35 HL145242, AI157155, AI141707, AI12893, AI083203, AI149928, AI095202, AI083203, GM136853, DK103126, and UL1 TR001439; the Dolly Parton COVID-19 Research Fund at Vanderbilt; RII COVID-19 Seed Grant 002196 from University of Arizona; a grant from Fast Grants, Mercatus Center, George Mason University; and funding from AstraZeneca. E.C.C. was supported by NIH grant T32 AI138932, and E.S.W. was supported by NIH grant F30 AI152327. J.E.C. is a recipient of the 2019 Future Insight Prize from Merck KGaA, which supported this work with a grant. Conceptualization, E.C.C. and J.E.C.; investigation, E.C.C. P.G. S.J.Z. N.S. M.S.D. E.S.W. C.R.C. C.A.T. S.L. S.K.C. E.B. J.K.W. S.D. L.M. A.T. J.R. R.E.S. E.D. and R.E.C.; writing first draft: E.C.C. and J.E.C.; all authors edited the manuscript and approved the final submission; supervision, B.J.D. R.H.C. C.A.T. M.S.D. and J.E.C.; funding acquisition, M.S.D. and J.E.C. E.D. J.K.W. and B.J.D. are employees of Integral Molecular, and B.J.D. is a shareholder in that company. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and Carnival Corporation and is on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory has received funding support in sponsored research agreements from AstraZeneca, IDBiologics, and Takeda. Funding Information: E.D., J.K.W., and B.J.D. are employees of Integral Molecular, and B.J.D. is a shareholder in that company. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and Carnival Corporation and is on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory has received funding support in sponsored research agreements from AstraZeneca, IDBiologics, and Takeda. Funding Information: EM data collection was collected at the Center for Structural Biology Cryo-EM facility at Vanderbilt University. We thank Cinque Soto for technical advice on study of public clonotypes. We thank Rachel Nargi, Joseph Reidy, Erica Armstrong, and Christopher Gainza for support in antibody purifications. We also thank Berkeley Lights and Jonathan Didier for expert technical support, and STEMCELL Technologies and Aida Mayhew for supplying crucial B cell enrichment reagents. We thank Jem Uhrlaub, Brendan Larson, and Dr. Mike Worobey (University of Arizona) for preparation and sequencing of early-passage SARS-CoV-2 stocks. We thank Eun-Hyung Lee, Doan C. Nguyen, and Ignacio Sanz from Emory University for sharing the plasmablast survival medium that promotes antibody secretion. We thank the anonymous donors of the plasma samples for their consent that allowed the WHO International standard for anti-SARS-CoV-2 human immunoglobulin to be prepared; we express our gratitude to those who have coordinated the collection of the convalescent plasma: Malcom Semple (University of Liverpool, UK), Lance Turtle (University of Liverpool, UK), Peter Openshaw (Imperial College London, UK), and Kenneth Baillie (University of Edinburgh) on behalf of the ISARIC4C Investigators; and Heli Harvala Simmonds and David Roberts (National Health Service Blood and Transplant, UK). We also thank NIBSC Standards Production and Development staff for the formulation and distribution of materials. We thank Chris Selverian for assistance in epitope mapping and Mallorie Fouch for S2 binding studies. This work was supported by Defense Advanced Research Projects Agency (DARPA) grants HR0011-18-2-0001 and HR0011-18-3-0001 ; US NIH contracts 75N93019C00074 , 75N93019C00062 , and 75N93019C00073 (to B.J.D.); NIH grants AI150739 , AI130591 , R35 HL145242 , AI157155 , AI141707 , AI12893 , AI083203 , AI149928 , AI095202 , AI083203 , GM136853 , DK103126 , and UL1 TR001439 ; the Dolly Parton COVID-19 Research Fund at Vanderbilt ; RII COVID-19 Seed Grant 002196 from University of Arizona ; a grant from Fast Grants, Mercatus Center, George Mason University ; and funding from AstraZeneca . E.C.C. was supported by NIH grant T32 AI138932 , and E.S.W. was supported by NIH grant F30 AI152327 . J.E.C. is a recipient of the 2019 Future Insight Prize from Merck KGaA , which supported this work with a grant. Publisher Copyright: © 2021 The Author(s)

PY - 2021/8/24

Y1 - 2021/8/24

N2 - Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases, as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identify 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, angiotensin-converting enzyme 2 [ACE2]-blocking clone that protects in vivo) and others recognizing non-RBD epitopes that bind the S2 domain. Germline-revertant forms of some public clonotypes bind efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.

AB - Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases, as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identify 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, angiotensin-converting enzyme 2 [ACE2]-blocking clone that protects in vivo) and others recognizing non-RBD epitopes that bind the S2 domain. Germline-revertant forms of some public clonotypes bind efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.

KW - COVID-19

KW - SARS-CoV

KW - SARS-CoV-2

KW - adaptive immunity

KW - antibodies

KW - coronavirus

KW - human

KW - monoclonal

KW - public clonotypes

KW - vaccines

UR - http://www.scopus.com/inward/record.url?scp=85113374536&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109604

DO - 10.1016/j.celrep.2021.109604

M3 - Article

C2 - 34411541

AN - SCOPUS:85113374536

SN - 2211-1247

VL - 36

JO - Cell Reports

JF - Cell Reports

IS - 8

M1 - 109604

ER -

Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

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