SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display

Roy A Ehling; Cédric R Weber; Derek M Mason; Simon Friedensohn; Bastian Wagner; Florian Bieberich; Edo Kapetanovic; Rodrigo Vazquez-Lombardi; Raphaël B Di Roberto; Kai-Lin Hong; Camille Wagner; Michele Pataia; Max D Overath; Daniel J Sheward; Ben Murrell; Alexander Yermanos; Andreas P Cuny; Miodrag Savic; Fabian Rudolf; Sai T Reddy

doi:10.1016/j.celrep.2021.110242

SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display

Roy A Ehling, Cédric R Weber, Derek M Mason, Simon Friedensohn, Bastian Wagner, Florian Bieberich, Edo Kapetanovic, Rodrigo Vazquez-Lombardi, Raphaël B Di Roberto, Kai-Lin Hong, Camille Wagner, Michele Pataia, Max D Overath, Daniel J Sheward, Ben Murrell, Alexander Yermanos, Andreas P Cuny, Miodrag Savic, Fabian Rudolf, Sai T Reddy^*

^*Corresponding author for this work

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

Abstract

Characterization of COVID-19 antibodies has largely focused on memory B cells; however, it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in resolving SARS-CoV-2 infection. Little is known about the specificity of plasma cells, largely because plasma cells lack surface antibody expression, thereby complicating their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and mammalian display to interrogate the specificity of plasma cells from 16 convalescent patients. Single-cell sequencing allows us to profile antibody repertoire features and identify expanded clonal lineages. Mammalian display screening is used to reveal that 43 antibodies (of 132 candidates) derived from expanded plasma cell lineages are specific to SARS-CoV-2 antigens, including antibodies with high affinity to the SARS-CoV-2 receptor-binding domain (RBD) that exhibit potent neutralization and broad binding to the RBD of SARS-CoV-2 variants (of concern/interest).

Original language	English
Article number	110242
Journal	Cell Reports
Volume	38
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2021.110242
Publication status	Published - 18 Jan 2022
Externally published	Yes

Keywords

Animals
Antibodies, Neutralizing/isolation & purification
Antibodies, Viral/isolation & purification
COVID-19/immunology
Cells, Cultured
Cohort Studies
Gene Library
HEK293 Cells
High-Throughput Nucleotide Sequencing/methods
Humans
Mammals
Neutralization Tests
Peptide Library
Plasma Cells/chemistry
SARS-CoV-2/immunology
Single-Cell Analysis/methods

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10.1016/j.celrep.2021.110242

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Ehling, R. A., Weber, C. R., Mason, D. M., Friedensohn, S., Wagner, B., Bieberich, F., Kapetanovic, E., Vazquez-Lombardi, R., Di Roberto, R. B., Hong, K.-L., Wagner, C., Pataia, M., Overath, M. D., Sheward, D. J., Murrell, B., Yermanos, A., Cuny, A. P., Savic, M., Rudolf, F., & Reddy, S. T. (2022). SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display. Cell Reports, 38(3), Article 110242. https://doi.org/10.1016/j.celrep.2021.110242

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title = "SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display",

abstract = "Characterization of COVID-19 antibodies has largely focused on memory B cells; however, it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in resolving SARS-CoV-2 infection. Little is known about the specificity of plasma cells, largely because plasma cells lack surface antibody expression, thereby complicating their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and mammalian display to interrogate the specificity of plasma cells from 16 convalescent patients. Single-cell sequencing allows us to profile antibody repertoire features and identify expanded clonal lineages. Mammalian display screening is used to reveal that 43 antibodies (of 132 candidates) derived from expanded plasma cell lineages are specific to SARS-CoV-2 antigens, including antibodies with high affinity to the SARS-CoV-2 receptor-binding domain (RBD) that exhibit potent neutralization and broad binding to the RBD of SARS-CoV-2 variants (of concern/interest).",

keywords = "Animals, Antibodies, Neutralizing/isolation & purification, Antibodies, Viral/isolation & purification, COVID-19/immunology, Cells, Cultured, Cohort Studies, Gene Library, HEK293 Cells, High-Throughput Nucleotide Sequencing/methods, Humans, Mammals, Neutralization Tests, Peptide Library, Plasma Cells/chemistry, SARS-CoV-2/immunology, Single-Cell Analysis/methods",

author = "Ehling, {Roy A} and Weber, {C{\'e}dric R} and Mason, {Derek M} and Simon Friedensohn and Bastian Wagner and Florian Bieberich and Edo Kapetanovic and Rodrigo Vazquez-Lombardi and {Di Roberto}, {Rapha{\"e}l B} and Kai-Lin Hong and Camille Wagner and Michele Pataia and Overath, {Max D} and Sheward, {Daniel J} and Ben Murrell and Alexander Yermanos and Cuny, {Andreas P} and Miodrag Savic and Fabian Rudolf and Reddy, {Sai T}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2022",

month = jan,

day = "18",

doi = "10.1016/j.celrep.2021.110242",

language = "English",

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Ehling, RA, Weber, CR, Mason, DM, Friedensohn, S, Wagner, B, Bieberich, F, Kapetanovic, E, Vazquez-Lombardi, R, Di Roberto, RB, Hong, K-L, Wagner, C, Pataia, M, Overath, MD, Sheward, DJ, Murrell, B, Yermanos, A, Cuny, AP, Savic, M, Rudolf, F & Reddy, ST 2022, 'SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display', Cell Reports, vol. 38, no. 3, 110242. https://doi.org/10.1016/j.celrep.2021.110242

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T1 - SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display

AU - Ehling, Roy A

AU - Weber, Cédric R

AU - Mason, Derek M

AU - Friedensohn, Simon

AU - Wagner, Bastian

AU - Bieberich, Florian

AU - Kapetanovic, Edo

AU - Vazquez-Lombardi, Rodrigo

AU - Di Roberto, Raphaël B

AU - Hong, Kai-Lin

AU - Wagner, Camille

AU - Pataia, Michele

AU - Overath, Max D

AU - Sheward, Daniel J

AU - Murrell, Ben

AU - Yermanos, Alexander

AU - Cuny, Andreas P

AU - Savic, Miodrag

AU - Rudolf, Fabian

AU - Reddy, Sai T

PY - 2022/1/18

Y1 - 2022/1/18

N2 - Characterization of COVID-19 antibodies has largely focused on memory B cells; however, it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in resolving SARS-CoV-2 infection. Little is known about the specificity of plasma cells, largely because plasma cells lack surface antibody expression, thereby complicating their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and mammalian display to interrogate the specificity of plasma cells from 16 convalescent patients. Single-cell sequencing allows us to profile antibody repertoire features and identify expanded clonal lineages. Mammalian display screening is used to reveal that 43 antibodies (of 132 candidates) derived from expanded plasma cell lineages are specific to SARS-CoV-2 antigens, including antibodies with high affinity to the SARS-CoV-2 receptor-binding domain (RBD) that exhibit potent neutralization and broad binding to the RBD of SARS-CoV-2 variants (of concern/interest).

AB - Characterization of COVID-19 antibodies has largely focused on memory B cells; however, it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in resolving SARS-CoV-2 infection. Little is known about the specificity of plasma cells, largely because plasma cells lack surface antibody expression, thereby complicating their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and mammalian display to interrogate the specificity of plasma cells from 16 convalescent patients. Single-cell sequencing allows us to profile antibody repertoire features and identify expanded clonal lineages. Mammalian display screening is used to reveal that 43 antibodies (of 132 candidates) derived from expanded plasma cell lineages are specific to SARS-CoV-2 antigens, including antibodies with high affinity to the SARS-CoV-2 receptor-binding domain (RBD) that exhibit potent neutralization and broad binding to the RBD of SARS-CoV-2 variants (of concern/interest).

KW - Animals

KW - Antibodies, Neutralizing/isolation & purification

KW - Antibodies, Viral/isolation & purification

KW - COVID-19/immunology

KW - Cells, Cultured

KW - Cohort Studies

KW - Gene Library

KW - HEK293 Cells

KW - High-Throughput Nucleotide Sequencing/methods

KW - Humans

KW - Mammals

KW - Neutralization Tests

KW - Peptide Library

KW - Plasma Cells/chemistry

KW - SARS-CoV-2/immunology

KW - Single-Cell Analysis/methods

U2 - 10.1016/j.celrep.2021.110242

DO - 10.1016/j.celrep.2021.110242

M3 - Article

C2 - 34998467

SN - 2211-1247

VL - 38

JO - Cell Reports

JF - Cell Reports

IS - 3

M1 - 110242

ER -

SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display

Abstract

Keywords

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