Discovery of neutralizing SARS-CoV-2 antibodies enriched in a unique antigen specific B cell cluster

Stine Sofie Frank Lende; Nanna Møller Barnkob; Randi Westh Hansen; Harsh Bansia; Mike Vestergaard; Frederik Holm Rothemejer; Anne Worsaae; Deijona Brown; Maria Lange Pedersen; Anna Halling Folkmar Rahimic; Anna Karina Juhl; Torben Gjetting; Lars Østergaard; Amédée Des Georges; Laurent-Michel Vuillard; Mariane Høgsbjerg Schleimann; Klaus Koefoed; Martin Tolstrup

doi:10.1371/journal.pone.0291131

Discovery of neutralizing SARS-CoV-2 antibodies enriched in a unique antigen specific B cell cluster

Stine Sofie Frank Lende^*, Nanna Møller Barnkob, Randi Westh Hansen, Harsh Bansia, Mike Vestergaard, Frederik Holm Rothemejer, Anne Worsaae, Deijona Brown, Maria Lange Pedersen, Anna Halling Folkmar Rahimic, Anna Karina Juhl, Torben Gjetting, Lars Østergaard, Amédée Des Georges, Laurent-Michel Vuillard, Mariane Høgsbjerg Schleimann, Klaus Koefoed, Martin Tolstrup^*

^*Corresponding author for this work

Department of Clinical Medicine - Department of Infectious Diseases

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

2 Citations (Scopus)

Abstract

Despite development of effective SARS-CoV-2 vaccines, a sub-group of vaccine non-responders depends on therapeutic antibodies or small-molecule drugs in cases of severe disease. However, perpetual viral evolution has required continuous efficacy monitoring as well as exploration of new therapeutic antibodies, to circumvent resistance mutations arising in the viral population. We performed SARS-CoV-2-specific B cell sorting and subsequent single-cell sequencing on material from 15 SARS-CoV-2 convalescent participants. Through screening of 455 monoclonal antibodies for SARS-CoV-2 variant binding and virus neutralization, we identified a cluster of activated B cells highly enriched for SARS-CoV-2 neutralizing antibodies. Epitope binning and Cryo-EM structure analysis identified the majority of neutralizing antibodies having epitopes overlapping with the ACE2 receptor binding motif (class 1 binders). Extensive functional antibody characterization identified two potent neutralizing antibodies, one retaining SARS-CoV-1 neutralizing capability, while both bind major common variants of concern and display prophylactic efficacy in vivo. The transcriptomic signature of activated B cells harboring broadly binding neutralizing antibodies with therapeutic potential identified here, may be a guide in future efforts of rapid therapeutic antibody discovery.

Original language	English
Article number	e0291131
Journal	PLOS ONE
Volume	18
Issue	9
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0291131
Publication status	Published - Sept 2023

Keywords

Humans
SARS-CoV-2
COVID-19 Vaccines
COVID-19
Blood Group Antigens
Antibodies, Viral
Antibodies, Neutralizing
Epitopes

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Lende, S. S. F., Barnkob, N. M., Hansen, R. W., Bansia, H., Vestergaard, M., Rothemejer, F. H., Worsaae, A., Brown, D., Pedersen, M. L., Rahimic, A. H. F., Juhl, A. K., Gjetting, T., Østergaard, L., Georges, A. D., Vuillard, L.-M., Schleimann, M. H., Koefoed, K., & Tolstrup, M. (2023). Discovery of neutralizing SARS-CoV-2 antibodies enriched in a unique antigen specific B cell cluster. PLOS ONE, 18(9), Article e0291131. https://doi.org/10.1371/journal.pone.0291131

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title = "Discovery of neutralizing SARS-CoV-2 antibodies enriched in a unique antigen specific B cell cluster",

abstract = "Despite development of effective SARS-CoV-2 vaccines, a sub-group of vaccine non-responders depends on therapeutic antibodies or small-molecule drugs in cases of severe disease. However, perpetual viral evolution has required continuous efficacy monitoring as well as exploration of new therapeutic antibodies, to circumvent resistance mutations arising in the viral population. We performed SARS-CoV-2-specific B cell sorting and subsequent single-cell sequencing on material from 15 SARS-CoV-2 convalescent participants. Through screening of 455 monoclonal antibodies for SARS-CoV-2 variant binding and virus neutralization, we identified a cluster of activated B cells highly enriched for SARS-CoV-2 neutralizing antibodies. Epitope binning and Cryo-EM structure analysis identified the majority of neutralizing antibodies having epitopes overlapping with the ACE2 receptor binding motif (class 1 binders). Extensive functional antibody characterization identified two potent neutralizing antibodies, one retaining SARS-CoV-1 neutralizing capability, while both bind major common variants of concern and display prophylactic efficacy in vivo. The transcriptomic signature of activated B cells harboring broadly binding neutralizing antibodies with therapeutic potential identified here, may be a guide in future efforts of rapid therapeutic antibody discovery.",

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author = "Lende, {Stine Sofie Frank} and Barnkob, {Nanna M{\o}ller} and Hansen, {Randi Westh} and Harsh Bansia and Mike Vestergaard and Rothemejer, {Frederik Holm} and Anne Worsaae and Deijona Brown and Pedersen, {Maria Lange} and Rahimic, {Anna Halling Folkmar} and Juhl, {Anna Karina} and Torben Gjetting and Lars {\O}stergaard and Georges, {Am{\'e}d{\'e}e Des} and Laurent-Michel Vuillard and Schleimann, {Mariane H{\o}gsbjerg} and Klaus Koefoed and Martin Tolstrup",

year = "2023",

month = sep,

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Lende, SSF, Barnkob, NM, Hansen, RW, Bansia, H, Vestergaard, M, Rothemejer, FH, Worsaae, A, Brown, D, Pedersen, ML , Rahimic, AHF , Juhl, AK, Gjetting, T, Østergaard, L, Georges, AD, Vuillard, L-M, Schleimann, MH, Koefoed, K & Tolstrup, M 2023, 'Discovery of neutralizing SARS-CoV-2 antibodies enriched in a unique antigen specific B cell cluster', PLOS ONE, vol. 18, no. 9, e0291131. https://doi.org/10.1371/journal.pone.0291131

Discovery of neutralizing SARS-CoV-2 antibodies enriched in a unique antigen specific B cell cluster. / Lende, Stine Sofie Frank; Barnkob, Nanna Møller; Hansen, Randi Westh et al.
In: PLOS ONE, Vol. 18, No. 9, e0291131, 09.2023.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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AU - Lende, Stine Sofie Frank

AU - Barnkob, Nanna Møller

AU - Hansen, Randi Westh

AU - Bansia, Harsh

AU - Vestergaard, Mike

AU - Rothemejer, Frederik Holm

AU - Worsaae, Anne

AU - Brown, Deijona

AU - Pedersen, Maria Lange

AU - Rahimic, Anna Halling Folkmar

AU - Juhl, Anna Karina

AU - Gjetting, Torben

AU - Østergaard, Lars

AU - Georges, Amédée Des

AU - Vuillard, Laurent-Michel

AU - Schleimann, Mariane Høgsbjerg

AU - Koefoed, Klaus

AU - Tolstrup, Martin

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N2 - Despite development of effective SARS-CoV-2 vaccines, a sub-group of vaccine non-responders depends on therapeutic antibodies or small-molecule drugs in cases of severe disease. However, perpetual viral evolution has required continuous efficacy monitoring as well as exploration of new therapeutic antibodies, to circumvent resistance mutations arising in the viral population. We performed SARS-CoV-2-specific B cell sorting and subsequent single-cell sequencing on material from 15 SARS-CoV-2 convalescent participants. Through screening of 455 monoclonal antibodies for SARS-CoV-2 variant binding and virus neutralization, we identified a cluster of activated B cells highly enriched for SARS-CoV-2 neutralizing antibodies. Epitope binning and Cryo-EM structure analysis identified the majority of neutralizing antibodies having epitopes overlapping with the ACE2 receptor binding motif (class 1 binders). Extensive functional antibody characterization identified two potent neutralizing antibodies, one retaining SARS-CoV-1 neutralizing capability, while both bind major common variants of concern and display prophylactic efficacy in vivo. The transcriptomic signature of activated B cells harboring broadly binding neutralizing antibodies with therapeutic potential identified here, may be a guide in future efforts of rapid therapeutic antibody discovery.

AB - Despite development of effective SARS-CoV-2 vaccines, a sub-group of vaccine non-responders depends on therapeutic antibodies or small-molecule drugs in cases of severe disease. However, perpetual viral evolution has required continuous efficacy monitoring as well as exploration of new therapeutic antibodies, to circumvent resistance mutations arising in the viral population. We performed SARS-CoV-2-specific B cell sorting and subsequent single-cell sequencing on material from 15 SARS-CoV-2 convalescent participants. Through screening of 455 monoclonal antibodies for SARS-CoV-2 variant binding and virus neutralization, we identified a cluster of activated B cells highly enriched for SARS-CoV-2 neutralizing antibodies. Epitope binning and Cryo-EM structure analysis identified the majority of neutralizing antibodies having epitopes overlapping with the ACE2 receptor binding motif (class 1 binders). Extensive functional antibody characterization identified two potent neutralizing antibodies, one retaining SARS-CoV-1 neutralizing capability, while both bind major common variants of concern and display prophylactic efficacy in vivo. The transcriptomic signature of activated B cells harboring broadly binding neutralizing antibodies with therapeutic potential identified here, may be a guide in future efforts of rapid therapeutic antibody discovery.

KW - Humans

KW - SARS-CoV-2

KW - COVID-19 Vaccines

KW - COVID-19

KW - Blood Group Antigens

KW - Antibodies, Viral

KW - Antibodies, Neutralizing

KW - Epitopes

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DO - 10.1371/journal.pone.0291131

M3 - Journal article

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SN - 1932-6203

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JO - PLOS ONE

JF - PLOS ONE

IS - 9

M1 - e0291131

ER -

Discovery of neutralizing SARS-CoV-2 antibodies enriched in a unique antigen specific B cell cluster

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