A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Hejun Liu; Meng Yuan; Deli Huang; Sandhya Bangaru; Fangzhu Zhao; Chang-Chun D. Lee; Linghang Peng; Shawn Barman; Xueyong Zhu; David Nemazee; Dennis R. Burton; Marit J. van Gils; Rogier W. Sanders; Hans-Christian Kornau; S. Momsen Reincke; Harald Prüss; Jakob Kreye; Nicholas C. Wu; Andrew B. Ward; Ian A. Wilson

doi:https://doi.org/10.1016/j.chom.2021.04.005

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Hejun Liu, Meng Yuan, Deli Huang, Sandhya Bangaru, Fangzhu Zhao, Chang-Chun D. Lee, Linghang Peng, Shawn Barman, Xueyong Zhu, David Nemazee, Dennis R. Burton, Marit J. van Gils, Rogier W. Sanders, Hans-Christian Kornau, S. Momsen Reincke, Harald Prüss, Jakob Kreye, Nicholas C. Wu, Andrew B. Ward, Ian A. Wilson

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

31 Citations (Scopus)

Abstract

Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.

Original language	English
Pages (from-to)	806-818.e6
Journal	CELL Host & Microbe
Volume	29
Issue number	5
DOIs	https://doi.org/10.1016/j.chom.2021.04.005
Publication status	Published - 12 May 2021

Keywords

3D structure
COVID-19
SARS-CoV-2
antibody cocktail
antibody-antigen interaction
coronavirus
cross-neutralizing antibody
crystallography
synergy

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https://doi.org/10.1016/j.chom.2021.04.005

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Liu, H., Yuan, M., Huang, D., Bangaru, S., Zhao, F., Lee, C.-C. D., Peng, L., Barman, S., Zhu, X., Nemazee, D., Burton, D. R., van Gils, M. J., Sanders, R. W., Kornau, H.-C., Reincke, S. M., Prüss, H., Kreye, J., Wu, N. C., Ward, A. B., & Wilson, I. A. (2021). A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection. CELL Host & Microbe, 29(5), 806-818.e6. https://doi.org/10.1016/j.chom.2021.04.005

@article{fc7e7e95d42441e0bcfffe36d6be938d,

title = "A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection",

abstract = "Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.",

keywords = "3D structure, COVID-19, SARS-CoV-2, antibody cocktail, antibody-antigen interaction, coronavirus, cross-neutralizing antibody, crystallography, synergy",

author = "Hejun Liu and Meng Yuan and Deli Huang and Sandhya Bangaru and Fangzhu Zhao and Lee, {Chang-Chun D.} and Linghang Peng and Shawn Barman and Xueyong Zhu and David Nemazee and Burton, {Dennis R.} and {van Gils}, {Marit J.} and Sanders, {Rogier W.} and Hans-Christian Kornau and Reincke, {S. Momsen} and Harald Pr{\"u}ss and Jakob Kreye and Wu, {Nicholas C.} and Ward, {Andrew B.} and Wilson, {Ian A.}",

note = "Funding Information: We thank Henry Tien for technical support with the crystallization robot, Jeanne Matteson and Yuanzi Hua for contribution to mammalian cell culture, Wenli Yu for insect cell culture, and Robyn Stanfield for assistance in data collection. We acknowledge BIAFFIN GmbH & Co KG (Kassel, Germany) for the help on the SPR competition assay. We are grateful to the staff of the Advanced Photon Source (APS) Beamline 23ID for assistance. This work was supported by the Bill and Melinda Gates Foundation OPP1170236 and INV-004923 (A.B.W., D.R.B., and I.A.W.), NIH R00 AI139445 (N.C.W.) and R01 AI132317 (D.N.), and the German Research Foundation (H.P.). R.W.S. is a recipient of a Vici fellowship from the Netherlands Organization for Scientific Research (NWO). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. Extraordinary facility operations were supported in part by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on the response to COVID-19, with funding provided by the Coronavirus CARES Act. Funding Information: We thank Henry Tien for technical support with the crystallization robot, Jeanne Matteson and Yuanzi Hua for contribution to mammalian cell culture, Wenli Yu for insect cell culture, and Robyn Stanfield for assistance in data collection. We acknowledge BIAFFIN GmbH & Co KG (Kassel, Germany) for the help on the SPR competition assay. We are grateful to the staff of the Advanced Photon Source (APS) Beamline 23ID for assistance. This work was supported by the Bill and Melinda Gates Foundation OPP1170236 and INV-004923 (A.B.W. D.R.B. and I.A.W.), NIH R00 AI139445 (N.C.W.) and R01 AI132317 (D.N.), and the German Research Foundation (H.P.). R.W.S. is a recipient of a Vici fellowship from the Netherlands Organization for Scientific Research (NWO). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. Extraordinary facility operations were supported in part by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on the response to COVID-19, with funding provided by the Coronavirus CARES Act. H.L. M.Y. N.C.W. and I.A.W. conceived and designed the study. H.L. M.Y. and C.-C.D.L. expressed and purified the proteins for crystallization and binding assay. D.H. F.Z. L.P. S. Barman, D.N. and D.R.B. provided neutralization data. S. Bangaru and A.B.W. provided nsEM data and reconstructions. H.-C.K. S.M.R. H.P. and J.K. provided CV38-142 antibody sequences and ELISA binding data. M.J.v.G. and R.W.S. provided COVA1-16 antibody sequences. H.L. M.Y. and X.Z. crystallized the antibody-antigen complexes and determined the crystal structures. H.L. M.Y. D.H. S. Bangaru, F.Z. N.C.W. H.-C.K. S.M.R. H.P. J.K. A.B.W. and I.A.W. analyzed the data. H.L. M.Y. N.C.W. and I.A.W. wrote the paper, and all authors reviewed and/or edited the paper. A patent application for SARS-CoV-2 antibody CV38-142 was first disclosed in (Kreye et al. 2020) and filed under application number 20182069.3 by some of the authors at Neurodegenerative Diseases (DZNE) and Charit?-Universit?tsmedizin Berlin. The Amsterdam UMC filed a patent on SARS-CoV-2 antibodies including COVA1-16 under application number 2020-039EP-PR that included the AMC authors on this paper. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = may,

day = "12",

doi = "https://doi.org/10.1016/j.chom.2021.04.005",

language = "English",

volume = "29",

pages = "806--818.e6",

journal = "CELL Host & Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "5",

}

Liu, H, Yuan, M, Huang, D, Bangaru, S, Zhao, F, Lee, C-CD, Peng, L, Barman, S, Zhu, X, Nemazee, D, Burton, DR, van Gils, MJ , Sanders, RW, Kornau, H-C, Reincke, SM, Prüss, H, Kreye, J, Wu, NC, Ward, AB & Wilson, IA 2021, 'A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection', CELL Host & Microbe, vol. 29, no. 5, pp. 806-818.e6. https://doi.org/10.1016/j.chom.2021.04.005

TY - JOUR

T1 - A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

AU - Liu, Hejun

AU - Yuan, Meng

AU - Huang, Deli

AU - Bangaru, Sandhya

AU - Zhao, Fangzhu

AU - Lee, Chang-Chun D.

AU - Peng, Linghang

AU - Barman, Shawn

AU - Zhu, Xueyong

AU - Nemazee, David

AU - Burton, Dennis R.

AU - van Gils, Marit J.

AU - Sanders, Rogier W.

AU - Kornau, Hans-Christian

AU - Reincke, S. Momsen

AU - Prüss, Harald

AU - Kreye, Jakob

AU - Wu, Nicholas C.

AU - Ward, Andrew B.

AU - Wilson, Ian A.

N1 - Funding Information: We thank Henry Tien for technical support with the crystallization robot, Jeanne Matteson and Yuanzi Hua for contribution to mammalian cell culture, Wenli Yu for insect cell culture, and Robyn Stanfield for assistance in data collection. We acknowledge BIAFFIN GmbH & Co KG (Kassel, Germany) for the help on the SPR competition assay. We are grateful to the staff of the Advanced Photon Source (APS) Beamline 23ID for assistance. This work was supported by the Bill and Melinda Gates Foundation OPP1170236 and INV-004923 (A.B.W., D.R.B., and I.A.W.), NIH R00 AI139445 (N.C.W.) and R01 AI132317 (D.N.), and the German Research Foundation (H.P.). R.W.S. is a recipient of a Vici fellowship from the Netherlands Organization for Scientific Research (NWO). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. Extraordinary facility operations were supported in part by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on the response to COVID-19, with funding provided by the Coronavirus CARES Act. Funding Information: We thank Henry Tien for technical support with the crystallization robot, Jeanne Matteson and Yuanzi Hua for contribution to mammalian cell culture, Wenli Yu for insect cell culture, and Robyn Stanfield for assistance in data collection. We acknowledge BIAFFIN GmbH & Co KG (Kassel, Germany) for the help on the SPR competition assay. We are grateful to the staff of the Advanced Photon Source (APS) Beamline 23ID for assistance. This work was supported by the Bill and Melinda Gates Foundation OPP1170236 and INV-004923 (A.B.W. D.R.B. and I.A.W.), NIH R00 AI139445 (N.C.W.) and R01 AI132317 (D.N.), and the German Research Foundation (H.P.). R.W.S. is a recipient of a Vici fellowship from the Netherlands Organization for Scientific Research (NWO). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. Extraordinary facility operations were supported in part by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on the response to COVID-19, with funding provided by the Coronavirus CARES Act. H.L. M.Y. N.C.W. and I.A.W. conceived and designed the study. H.L. M.Y. and C.-C.D.L. expressed and purified the proteins for crystallization and binding assay. D.H. F.Z. L.P. S. Barman, D.N. and D.R.B. provided neutralization data. S. Bangaru and A.B.W. provided nsEM data and reconstructions. H.-C.K. S.M.R. H.P. and J.K. provided CV38-142 antibody sequences and ELISA binding data. M.J.v.G. and R.W.S. provided COVA1-16 antibody sequences. H.L. M.Y. and X.Z. crystallized the antibody-antigen complexes and determined the crystal structures. H.L. M.Y. D.H. S. Bangaru, F.Z. N.C.W. H.-C.K. S.M.R. H.P. J.K. A.B.W. and I.A.W. analyzed the data. H.L. M.Y. N.C.W. and I.A.W. wrote the paper, and all authors reviewed and/or edited the paper. A patent application for SARS-CoV-2 antibody CV38-142 was first disclosed in (Kreye et al. 2020) and filed under application number 20182069.3 by some of the authors at Neurodegenerative Diseases (DZNE) and Charit?-Universit?tsmedizin Berlin. The Amsterdam UMC filed a patent on SARS-CoV-2 antibodies including COVA1-16 under application number 2020-039EP-PR that included the AMC authors on this paper. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/5/12

Y1 - 2021/5/12

N2 - Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.

AB - Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.

KW - 3D structure

KW - COVID-19

KW - SARS-CoV-2

KW - antibody cocktail

KW - antibody-antigen interaction

KW - coronavirus

KW - cross-neutralizing antibody

KW - crystallography

KW - synergy

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U2 - https://doi.org/10.1016/j.chom.2021.04.005

DO - https://doi.org/10.1016/j.chom.2021.04.005

M3 - Article

C2 - 33894127

SN - 1931-3128

VL - 29

SP - 806-818.e6

JO - CELL Host & Microbe

JF - CELL Host & Microbe

IS - 5

ER -

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Abstract

Keywords

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