A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants

Aaron J. Schmitz; Jackson S. Turner; Zhuoming Liu; Julian Q. Zhou; Ishmael D. Aziati; Rita E. Chen; Astha Joshi; Traci L. Bricker; Tamarand L. Darling; Daniel C. Adelsberg; Clara G. Altomare; Wafaa B. Alsoussi; James Brett Case; Laura A. VanBlargan; Tingting Lei; Mahima Thapa; Fatima Amanat; Trushar Jeevan; Thomas Fabrizio; Jane A. O'Halloran; Pei Yong Shi; Rachel M. Presti; Richard J. Webby; Florian Krammer; Sean P.J. Whelan; Goran Bajic; Michael S. Diamond; Adrianus C.M. Boon; Ali H. Ellebedy

doi:10.1016/j.immuni.2021.08.013

A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants

Aaron J. Schmitz, Jackson S. Turner, Zhuoming Liu, Julian Q. Zhou, Ishmael D. Aziati, Rita E. Chen, Astha Joshi, Traci L. Bricker, Tamarand L. Darling, Daniel C. Adelsberg, Clara G. Altomare, Wafaa B. Alsoussi, James Brett Case, Laura A. VanBlargan, Tingting Lei, Mahima Thapa, Fatima Amanat, Trushar Jeevan, Thomas Fabrizio, Jane A. O'HalloranPei Yong Shi, Rachel M. Presti, Richard J. Webby, Florian Krammer, Sean P.J. Whelan, Goran Bajic, Michael S. Diamond, Adrianus C.M. Boon, Ali H. Ellebedy

Biochemistry & Molecular Biology

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

32 Scopus citations

Abstract

The emergence of SARS-CoV-2 antigenic variants with increased transmissibility is a public health threat. Some variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies. Here, we analyzed receptor binding domain-binding monoclonal antibodies derived from SARS-CoV-2 mRNA vaccine-elicited germinal center B cells for neutralizing activity against the WA1/2020 D614G SARS-CoV-2 strain and variants of concern. Of five monoclonal antibodies that potently neutralized the WA1/2020 D614G strain, all retained neutralizing capacity against the B.1.617.2 variant, four also neutralized the B.1.1.7 variant, and only one, 2C08, also neutralized the B.1.351 and B.1.1.28 variants. 2C08 reduced lung viral load and morbidity in hamsters challenged with the WA1/2020 D614G, B.1.351, or B.1.617.2 strains. Clonal analysis identified 2C08-like public clonotypes among B cells responding to SARS-CoV-2 infection or vaccination in 41 out of 181 individuals. Thus, 2C08-like antibodies can be induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.

Original language	English (US)
Pages (from-to)	2159-2166.e6
Journal	Immunity
Volume	54
Issue number	9
DOIs	https://doi.org/10.1016/j.immuni.2021.08.013
State	Published - Sep 14 2021

Keywords

B cell
SARS-CoV-2
germinal center
hamster
lymph node
mRNA vaccine
neutralizing antibodies
public clone
receptor binding domain
spike protein

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/j.immuni.2021.08.013

Cite this

Schmitz, A. J., Turner, J. S., Liu, Z., Zhou, J. Q., Aziati, I. D., Chen, R. E., Joshi, A., Bricker, T. L., Darling, T. L., Adelsberg, D. C., Altomare, C. G., Alsoussi, W. B., Case, J. B., VanBlargan, L. A., Lei, T., Thapa, M., Amanat, F., Jeevan, T., Fabrizio, T., ... Ellebedy, A. H. (2021). A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants. Immunity, 54(9), 2159-2166.e6. https://doi.org/10.1016/j.immuni.2021.08.013

Schmitz, AJ, Turner, JS, Liu, Z, Zhou, JQ, Aziati, ID, Chen, RE, Joshi, A, Bricker, TL, Darling, TL, Adelsberg, DC, Altomare, CG, Alsoussi, WB, Case, JB, VanBlargan, LA, Lei, T, Thapa, M, Amanat, F, Jeevan, T, Fabrizio, T, O'Halloran, JA, Shi, PY, Presti, RM, Webby, RJ, Krammer, F, Whelan, SPJ, Bajic, G, Diamond, MS, Boon, ACM & Ellebedy, AH 2021, 'A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants', Immunity, vol. 54, no. 9, pp. 2159-2166.e6. https://doi.org/10.1016/j.immuni.2021.08.013

@article{003eec0096bb4250b79864f33743f9ab,

title = "A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants",

abstract = "The emergence of SARS-CoV-2 antigenic variants with increased transmissibility is a public health threat. Some variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies. Here, we analyzed receptor binding domain-binding monoclonal antibodies derived from SARS-CoV-2 mRNA vaccine-elicited germinal center B cells for neutralizing activity against the WA1/2020 D614G SARS-CoV-2 strain and variants of concern. Of five monoclonal antibodies that potently neutralized the WA1/2020 D614G strain, all retained neutralizing capacity against the B.1.617.2 variant, four also neutralized the B.1.1.7 variant, and only one, 2C08, also neutralized the B.1.351 and B.1.1.28 variants. 2C08 reduced lung viral load and morbidity in hamsters challenged with the WA1/2020 D614G, B.1.351, or B.1.617.2 strains. Clonal analysis identified 2C08-like public clonotypes among B cells responding to SARS-CoV-2 infection or vaccination in 41 out of 181 individuals. Thus, 2C08-like antibodies can be induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.",

keywords = "B cell, SARS-CoV-2, germinal center, hamster, lymph node, mRNA vaccine, neutralizing antibodies, public clone, receptor binding domain, spike protein",

author = "Schmitz, {Aaron J.} and Turner, {Jackson S.} and Zhuoming Liu and Zhou, {Julian Q.} and Aziati, {Ishmael D.} and Chen, {Rita E.} and Astha Joshi and Bricker, {Traci L.} and Darling, {Tamarand L.} and Adelsberg, {Daniel C.} and Altomare, {Clara G.} and Alsoussi, {Wafaa B.} and Case, {James Brett} and VanBlargan, {Laura A.} and Tingting Lei and Mahima Thapa and Fatima Amanat and Trushar Jeevan and Thomas Fabrizio and O'Halloran, {Jane A.} and Shi, {Pei Yong} and Presti, {Rachel M.} and Webby, {Richard J.} and Florian Krammer and Whelan, {Sean P.J.} and Goran Bajic and Diamond, {Michael S.} and Boon, {Adrianus C.M.} and Ellebedy, {Ali H.}",

note = "Funding Information: The Vero-TMPRSS2 cells were kindly provided by S. Ding (Washington University School of Medicine, St. Louis, MO). The clinical sample for isolation of the B.1.617.2 variant was kindly provided by A. Patel (Poplar Healthcare, Memphis, TN). We thank W. Kim for helpful discussions. Some of this work was performed at the National Center for CryoEM Access and Training (NCCAT) and the Simons Electron Microscopy Center located at the New York Structural Biology Center, supported by the NIH Common Fund Transformative High Resolution Cryo-Electron Microscopy program ( U24 GM129539 ) and by grants from the Simons Foundation ( SF349247 ) and NY State Assembly Majority . The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIAID or NIH. The Ellebedy laboratory was supported by NIAID grants U01AI141990 and U01AI150747 and NIAID Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400006C . The Ellebedy and Krammer laboratories were supported by NIAID Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400008C and NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051 . The Diamond laboratory was supported by NIH contract 75N93019C00062 and grant R01 AI157155 . The Boon laboratory was supported by NIH grants R01-AI118938 and U01-AI151810 and the Children's Discovery Institute grant PDII2018702 . The Webby laboratory was supported by the NIAID Centers of Excellence for Influenza Research and Response contract 75N93021C00016 . The Shi laboratory was supported by NIH grants AI134907 and UL1TR001439 and awards from the Sealy & Smith Foundation, Kleberg Foundation , the John S. Dunn Foundation , the Amon G. Carter Foundation , the Gilson Longenbaugh Foundation , and the Summerfield Roberts Foundation . The SARS-CoV-2 vaccine study was in part supported by NIH/National Center for Advancing Translational Sciences grant UL1 TR002345 . J.S.T. was supported by NIAID 5T32CA009547 . J.B.C. was supported by a Helen Hay Whitney postdoctoral fellowship . Funding Information: The Ellebedy laboratory received funding under sponsored research agreements that are unrelated to the data presented in the current study from Emergent BioSolutions and from AbbVie. A.H.E. is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting LLC. M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, Carnival Corporation and on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received unrelated sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences Inc., and Nano targeting & Therapy Biopharma Inc. The Boon laboratory has received funding support from AbbVie Inc., for the commercial development of a SARS-CoV-2 mAb. A.J.S., J.S.T., W.B.A., J.B.C., S.P.J.W., M.S.D., A.C.M.B., and A.H.E. are recipients of a licensing agreement with Abbvie Inc., for commercial development of a SARS-CoV-2 mAb. A patent application related to this work has been filed by Washington University School of Medicine. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list Florian Krammer as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. Florian Krammer has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. The Shi laboratory has received sponsored research agreements from Pfizer, Gilead, Merck, and IGM Sciences Inc. The Whelan laboratory has received unrelated funding support in sponsored research agreements with Vir Biotechnology, AbbVie, and sAB therapeutics. All other authors declare no conflict of interest. Funding Information: The Vero-TMPRSS2 cells were kindly provided by S. Ding (Washington University School of Medicine, St. Louis, MO). The clinical sample for isolation of the B.1.617.2 variant was kindly provided by A. Patel (Poplar Healthcare, Memphis, TN). We thank W. Kim for helpful discussions. Some of this work was performed at the National Center for CryoEM Access and Training (NCCAT) and the Simons Electron Microscopy Center located at the New York Structural Biology Center, supported by the NIH Common Fund Transformative High Resolution Cryo-Electron Microscopy program (U24 GM129539) and by grants from the Simons Foundation (SF349247) and NY State Assembly Majority. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIAID or NIH. The Ellebedy laboratory was supported by NIAID grants U01AI141990 and U01AI150747 and NIAID Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400006C. The Ellebedy and Krammer laboratories were supported by NIAID Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400008C and NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051. The Diamond laboratory was supported by NIH contract 75N93019C00062 and grant R01 AI157155. The Boon laboratory was supported by NIH grants R01-AI118938 and U01-AI151810 and the Children's Discovery Institute grant PDII2018702. The Webby laboratory was supported by the NIAID Centers of Excellence for Influenza Research and Response contract 75N93021C00016. The Shi laboratory was supported by NIH grants AI134907 and UL1TR001439 and awards from the Sealy & Smith Foundation, Kleberg Foundation, the John S. Dunn Foundation, the Amon G. Carter Foundation, the Gilson Longenbaugh Foundation, and the Summerfield Roberts Foundation. The SARS-CoV-2 vaccine study was in part supported by NIH/National Center for Advancing Translational Sciences grant UL1 TR002345. J.S.T. was supported by NIAID 5T32CA009547. J.B.C. was supported by a Helen Hay Whitney postdoctoral fellowship. A.J.S. and J.S.T. isolated the antibodies. A.J.S. Z.L. I.D.A. R.E.C. A.J. T.L.B. T.L.D. W.B.A. J.B.C, and L.A.V. functionally characterized the mAbs in vitro and in vivo. J.Q.Z. analyzed BCR repertoire data. D.C.A. and C.G.A. performed structural analyses. T.L. M.T. and F.A. expressed and purified the mAbs and recombinant viral proteins. T.J. and T.F. isolated the B.1.617.2 variant virus. A.J.S. and J.S.T. compiled and analyzed data. J.A.O. and R.M.P. supervised the vaccination study. P.-Y.S. R.J.W. and F.K. provided critical reagents. S.P.J.W. supervised the mapping analysis. G.B. supervised the structural analysis. M.S.D. and A.C.M.B. supervised the in vitro and in vivo analyses, respectively. A.H.E. conceptualized the study and wrote the manuscript with input from all co-authors. The Ellebedy laboratory received funding under sponsored research agreements that are unrelated to the data presented in the current study from Emergent BioSolutions and from AbbVie. A.H.E. is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting LLC. M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, Carnival Corporation and on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received unrelated sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences Inc. and Nano targeting & Therapy Biopharma Inc. The Boon laboratory has received funding support from AbbVie Inc. for the commercial development of a SARS-CoV-2 mAb. A.J.S. J.S.T. W.B.A. J.B.C. S.P.J.W. M.S.D. A.C.M.B. and A.H.E. are recipients of a licensing agreement with Abbvie Inc. for commercial development of a SARS-CoV-2 mAb. A patent application related to this work has been filed by Washington University School of Medicine. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list Florian Krammer as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. Florian Krammer has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. The Shi laboratory has received sponsored research agreements from Pfizer, Gilead, Merck, and IGM Sciences Inc. The Whelan laboratory has received unrelated funding support in sponsored research agreements with Vir Biotechnology, AbbVie, and sAB therapeutics. All other authors declare no conflict of interest. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = sep,

day = "14",

doi = "10.1016/j.immuni.2021.08.013",

language = "English (US)",

volume = "54",

pages = "2159--2166.e6",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "9",

}

TY - JOUR

T1 - A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants

AU - Schmitz, Aaron J.

AU - Turner, Jackson S.

AU - Liu, Zhuoming

AU - Zhou, Julian Q.

AU - Aziati, Ishmael D.

AU - Chen, Rita E.

AU - Joshi, Astha

AU - Bricker, Traci L.

AU - Darling, Tamarand L.

AU - Adelsberg, Daniel C.

AU - Altomare, Clara G.

AU - Alsoussi, Wafaa B.

AU - Case, James Brett

AU - VanBlargan, Laura A.

AU - Lei, Tingting

AU - Thapa, Mahima

AU - Amanat, Fatima

AU - Jeevan, Trushar

AU - Fabrizio, Thomas

AU - O'Halloran, Jane A.

AU - Shi, Pei Yong

AU - Presti, Rachel M.

AU - Webby, Richard J.

AU - Krammer, Florian

AU - Whelan, Sean P.J.

AU - Bajic, Goran

AU - Diamond, Michael S.

AU - Boon, Adrianus C.M.

AU - Ellebedy, Ali H.

N1 - Funding Information: The Vero-TMPRSS2 cells were kindly provided by S. Ding (Washington University School of Medicine, St. Louis, MO). The clinical sample for isolation of the B.1.617.2 variant was kindly provided by A. Patel (Poplar Healthcare, Memphis, TN). We thank W. Kim for helpful discussions. Some of this work was performed at the National Center for CryoEM Access and Training (NCCAT) and the Simons Electron Microscopy Center located at the New York Structural Biology Center, supported by the NIH Common Fund Transformative High Resolution Cryo-Electron Microscopy program ( U24 GM129539 ) and by grants from the Simons Foundation ( SF349247 ) and NY State Assembly Majority . The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIAID or NIH. The Ellebedy laboratory was supported by NIAID grants U01AI141990 and U01AI150747 and NIAID Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400006C . The Ellebedy and Krammer laboratories were supported by NIAID Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400008C and NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051 . The Diamond laboratory was supported by NIH contract 75N93019C00062 and grant R01 AI157155 . The Boon laboratory was supported by NIH grants R01-AI118938 and U01-AI151810 and the Children's Discovery Institute grant PDII2018702 . The Webby laboratory was supported by the NIAID Centers of Excellence for Influenza Research and Response contract 75N93021C00016 . The Shi laboratory was supported by NIH grants AI134907 and UL1TR001439 and awards from the Sealy & Smith Foundation, Kleberg Foundation , the John S. Dunn Foundation , the Amon G. Carter Foundation , the Gilson Longenbaugh Foundation , and the Summerfield Roberts Foundation . The SARS-CoV-2 vaccine study was in part supported by NIH/National Center for Advancing Translational Sciences grant UL1 TR002345 . J.S.T. was supported by NIAID 5T32CA009547 . J.B.C. was supported by a Helen Hay Whitney postdoctoral fellowship . Funding Information: The Ellebedy laboratory received funding under sponsored research agreements that are unrelated to the data presented in the current study from Emergent BioSolutions and from AbbVie. A.H.E. is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting LLC. M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, Carnival Corporation and on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received unrelated sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences Inc., and Nano targeting & Therapy Biopharma Inc. The Boon laboratory has received funding support from AbbVie Inc., for the commercial development of a SARS-CoV-2 mAb. A.J.S., J.S.T., W.B.A., J.B.C., S.P.J.W., M.S.D., A.C.M.B., and A.H.E. are recipients of a licensing agreement with Abbvie Inc., for commercial development of a SARS-CoV-2 mAb. A patent application related to this work has been filed by Washington University School of Medicine. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list Florian Krammer as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. Florian Krammer has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. The Shi laboratory has received sponsored research agreements from Pfizer, Gilead, Merck, and IGM Sciences Inc. The Whelan laboratory has received unrelated funding support in sponsored research agreements with Vir Biotechnology, AbbVie, and sAB therapeutics. All other authors declare no conflict of interest. Funding Information: The Vero-TMPRSS2 cells were kindly provided by S. Ding (Washington University School of Medicine, St. Louis, MO). The clinical sample for isolation of the B.1.617.2 variant was kindly provided by A. Patel (Poplar Healthcare, Memphis, TN). We thank W. Kim for helpful discussions. Some of this work was performed at the National Center for CryoEM Access and Training (NCCAT) and the Simons Electron Microscopy Center located at the New York Structural Biology Center, supported by the NIH Common Fund Transformative High Resolution Cryo-Electron Microscopy program (U24 GM129539) and by grants from the Simons Foundation (SF349247) and NY State Assembly Majority. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIAID or NIH. The Ellebedy laboratory was supported by NIAID grants U01AI141990 and U01AI150747 and NIAID Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400006C. The Ellebedy and Krammer laboratories were supported by NIAID Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400008C and NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051. The Diamond laboratory was supported by NIH contract 75N93019C00062 and grant R01 AI157155. The Boon laboratory was supported by NIH grants R01-AI118938 and U01-AI151810 and the Children's Discovery Institute grant PDII2018702. The Webby laboratory was supported by the NIAID Centers of Excellence for Influenza Research and Response contract 75N93021C00016. The Shi laboratory was supported by NIH grants AI134907 and UL1TR001439 and awards from the Sealy & Smith Foundation, Kleberg Foundation, the John S. Dunn Foundation, the Amon G. Carter Foundation, the Gilson Longenbaugh Foundation, and the Summerfield Roberts Foundation. The SARS-CoV-2 vaccine study was in part supported by NIH/National Center for Advancing Translational Sciences grant UL1 TR002345. J.S.T. was supported by NIAID 5T32CA009547. J.B.C. was supported by a Helen Hay Whitney postdoctoral fellowship. A.J.S. and J.S.T. isolated the antibodies. A.J.S. Z.L. I.D.A. R.E.C. A.J. T.L.B. T.L.D. W.B.A. J.B.C, and L.A.V. functionally characterized the mAbs in vitro and in vivo. J.Q.Z. analyzed BCR repertoire data. D.C.A. and C.G.A. performed structural analyses. T.L. M.T. and F.A. expressed and purified the mAbs and recombinant viral proteins. T.J. and T.F. isolated the B.1.617.2 variant virus. A.J.S. and J.S.T. compiled and analyzed data. J.A.O. and R.M.P. supervised the vaccination study. P.-Y.S. R.J.W. and F.K. provided critical reagents. S.P.J.W. supervised the mapping analysis. G.B. supervised the structural analysis. M.S.D. and A.C.M.B. supervised the in vitro and in vivo analyses, respectively. A.H.E. conceptualized the study and wrote the manuscript with input from all co-authors. The Ellebedy laboratory received funding under sponsored research agreements that are unrelated to the data presented in the current study from Emergent BioSolutions and from AbbVie. A.H.E. is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting LLC. M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, Carnival Corporation and on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received unrelated sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences Inc. and Nano targeting & Therapy Biopharma Inc. The Boon laboratory has received funding support from AbbVie Inc. for the commercial development of a SARS-CoV-2 mAb. A.J.S. J.S.T. W.B.A. J.B.C. S.P.J.W. M.S.D. A.C.M.B. and A.H.E. are recipients of a licensing agreement with Abbvie Inc. for commercial development of a SARS-CoV-2 mAb. A patent application related to this work has been filed by Washington University School of Medicine. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list Florian Krammer as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. Florian Krammer has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. The Shi laboratory has received sponsored research agreements from Pfizer, Gilead, Merck, and IGM Sciences Inc. The Whelan laboratory has received unrelated funding support in sponsored research agreements with Vir Biotechnology, AbbVie, and sAB therapeutics. All other authors declare no conflict of interest. Publisher Copyright: © 2021 Elsevier Inc.

PY - 2021/9/14

Y1 - 2021/9/14

N2 - The emergence of SARS-CoV-2 antigenic variants with increased transmissibility is a public health threat. Some variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies. Here, we analyzed receptor binding domain-binding monoclonal antibodies derived from SARS-CoV-2 mRNA vaccine-elicited germinal center B cells for neutralizing activity against the WA1/2020 D614G SARS-CoV-2 strain and variants of concern. Of five monoclonal antibodies that potently neutralized the WA1/2020 D614G strain, all retained neutralizing capacity against the B.1.617.2 variant, four also neutralized the B.1.1.7 variant, and only one, 2C08, also neutralized the B.1.351 and B.1.1.28 variants. 2C08 reduced lung viral load and morbidity in hamsters challenged with the WA1/2020 D614G, B.1.351, or B.1.617.2 strains. Clonal analysis identified 2C08-like public clonotypes among B cells responding to SARS-CoV-2 infection or vaccination in 41 out of 181 individuals. Thus, 2C08-like antibodies can be induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.

AB - The emergence of SARS-CoV-2 antigenic variants with increased transmissibility is a public health threat. Some variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies. Here, we analyzed receptor binding domain-binding monoclonal antibodies derived from SARS-CoV-2 mRNA vaccine-elicited germinal center B cells for neutralizing activity against the WA1/2020 D614G SARS-CoV-2 strain and variants of concern. Of five monoclonal antibodies that potently neutralized the WA1/2020 D614G strain, all retained neutralizing capacity against the B.1.617.2 variant, four also neutralized the B.1.1.7 variant, and only one, 2C08, also neutralized the B.1.351 and B.1.1.28 variants. 2C08 reduced lung viral load and morbidity in hamsters challenged with the WA1/2020 D614G, B.1.351, or B.1.617.2 strains. Clonal analysis identified 2C08-like public clonotypes among B cells responding to SARS-CoV-2 infection or vaccination in 41 out of 181 individuals. Thus, 2C08-like antibodies can be induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.

KW - B cell

KW - SARS-CoV-2

KW - germinal center

KW - hamster

KW - lymph node

KW - mRNA vaccine

KW - neutralizing antibodies

KW - public clone

KW - receptor binding domain

KW - spike protein

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UR - http://www.scopus.com/inward/citedby.url?scp=85113975510&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2021.08.013

DO - 10.1016/j.immuni.2021.08.013

M3 - Article

C2 - 34464596

AN - SCOPUS:85113975510

SN - 1074-7613

VL - 54

SP - 2159-2166.e6

JO - Immunity

JF - Immunity

IS - 9

ER -

A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants

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