Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire

Rafael D. Melani; Benjamin J. Des Soye; Jared O. Kafader; Eleonora Forte; Michael Hollas; Voislav Blagojevic; Fernanda Negrão; John P. McGee; Bryon Drown; Cameron Lloyd-Jones; Henrique S. Seckler; Jeannie M. Camarillo; Philip D. Compton; Richard D. LeDuc; Bryan Early; Ryan T. Fellers; Byoung Kyu Cho; Basil Baby Mattamana; Young Ah Goo; Paul M. Thomas; Michelle K. Ash; Pavan P. Bhimalli; Lena Al-Harthi; Beverly E. Sha; Jeffrey R. Schneider; Neil L. Kelleher

doi:10.1021/acs.jproteome.1c00882

Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire

Rafael D. Melani, Benjamin J. Des Soye, Jared O. Kafader, Eleonora Forte, Michael Hollas, Voislav Blagojevic, Fernanda Negrão, John P. McGee, Bryon Drown, Cameron Lloyd-Jones, Henrique S. Seckler, Jeannie M. Camarillo, Philip D. Compton, Richard D. LeDuc, Bryan Early, Ryan T. Fellers, Byoung Kyu Cho, Basil Baby Mattamana, Young Ah Goo, Paul M. ThomasMichelle K. Ash, Pavan P. Bhimalli, Lena Al-Harthi, Beverly E. Sha, Jeffrey R. Schneider, Neil L. Kelleher^*

^*Corresponding author for this work

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

22 Scopus citations

Abstract

Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We applied Ig-MS to plasma from subjects with severe and mild COVID-19 and immunized subjects after two vaccine doses, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, that could use other antigens of interest to gauge immune responses to vaccination, pathogens, or autoimmune disorders.

Original language	English (US)
Pages (from-to)	274-288
Number of pages	15
Journal	Journal of Proteome Research
Volume	21
Issue number	1
DOIs	https://doi.org/10.1021/acs.jproteome.1c00882
State	Published - Jan 7 2022

Funding

RBD was expressed by the Northwestern Recombinant Protein Production Core Facility. The reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Vector pCAGGS Containing the SARS-Related Coronavirus 2, Wuhan-Hu-1 Spike Glycoprotein Receptor-Binding Domain (RBD), NR-52309. IgG glycosylation and bottom-up proteomics were measured by the Northwestern Proteomics Core Facility. This study was funded by the National Institute of Health under a grant from the National Institute of General Medical Sciences P41 GM108569 (N.L.K.); the Research Corporation (Grant no. 27372, N.L.K. and E.F.); Administrative Supplement to SBIR grant number R44 GM121130 (P.D.C.); Walder Foundation grant number SCI16 (J.R.S.); the NIH Office of Director award S10 OD025194 (P.D.C.); the Northwestern Medicine Dr. Michael M. Abecassis Transplant Innovation Endowment Grant; NCI CCSG P30 CA060553 (awarded to the Robert H. Lurie Comprehensive Cancer Center). National Cancer Institute grant 1F32CA246894-01A1 (B.D.); The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Keywords

COVID-19
SARS-CoV-2
antibodies
individual ion mass spectrometry
proteomics
serology
top-down mass spectrometry

ASJC Scopus subject areas

General Chemistry
Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acs.jproteome.1c00882

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Melani, R. D., Des Soye, B. J., Kafader, J. O., Forte, E., Hollas, M., Blagojevic, V., Negrão, F., McGee, J. P., Drown, B., Lloyd-Jones, C., Seckler, H. S., Camarillo, J. M., Compton, P. D., LeDuc, R. D., Early, B., Fellers, R. T., Cho, B. K., Mattamana, B. B., Goo, Y. A., ... Kelleher, N. L. (2022). Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire. Journal of Proteome Research, 21(1), 274-288. https://doi.org/10.1021/acs.jproteome.1c00882

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title = "Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire",

abstract = "Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We applied Ig-MS to plasma from subjects with severe and mild COVID-19 and immunized subjects after two vaccine doses, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, that could use other antigens of interest to gauge immune responses to vaccination, pathogens, or autoimmune disorders.",

keywords = "COVID-19, SARS-CoV-2, antibodies, individual ion mass spectrometry, proteomics, serology, top-down mass spectrometry",

author = "Melani, {Rafael D.} and {Des Soye}, {Benjamin J.} and Kafader, {Jared O.} and Eleonora Forte and Michael Hollas and Voislav Blagojevic and Fernanda Negr{\~a}o and McGee, {John P.} and Bryon Drown and Cameron Lloyd-Jones and Seckler, {Henrique S.} and Camarillo, {Jeannie M.} and Compton, {Philip D.} and LeDuc, {Richard D.} and Bryan Early and Fellers, {Ryan T.} and Cho, {Byoung Kyu} and Mattamana, {Basil Baby} and Goo, {Young Ah} and Thomas, {Paul M.} and Ash, {Michelle K.} and Bhimalli, {Pavan P.} and Lena Al-Harthi and Sha, {Beverly E.} and Schneider, {Jeffrey R.} and Kelleher, {Neil L.}",

note = "Funding Information: RBD was expressed by the Northwestern Recombinant Protein Production Core Facility. The reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Vector pCAGGS Containing the SARS-Related Coronavirus 2, Wuhan-Hu-1 Spike Glycoprotein Receptor-Binding Domain (RBD), NR-52309. IgG glycosylation and bottom-up proteomics were measured by the Northwestern Proteomics Core Facility. This study was funded by the National Institute of Health under a grant from the National Institute of General Medical Sciences P41 GM108569 (N.L.K.); the Research Corporation (Grant no. 27372, N.L.K. and E.F.); Administrative Supplement to SBIR grant number R44 GM121130 (P.D.C.); Walder Foundation grant number SCI16 (J.R.S.); the NIH Office of Director award S10 OD025194 (P.D.C.); the Northwestern Medicine Dr. Michael M. Abecassis Transplant Innovation Endowment Grant; NCI CCSG P30 CA060553 (awarded to the Robert H. Lurie Comprehensive Cancer Center). National Cancer Institute grant 1F32CA246894-01A1 (B.D.); The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2021 American Chemical Society",

year = "2022",

month = jan,

day = "7",

doi = "10.1021/acs.jproteome.1c00882",

language = "English (US)",

volume = "21",

pages = "274--288",

journal = "Journal of Proteome Research",

issn = "1535-3893",

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Melani, RD, Des Soye, BJ, Kafader, JO, Forte, E, Hollas, M, Blagojevic, V, Negrão, F, McGee, JP, Drown, B, Lloyd-Jones, C, Seckler, HS, Camarillo, JM, Compton, PD, LeDuc, RD, Early, B, Fellers, RT, Cho, BK, Mattamana, BB, Goo, YA, Thomas, PM, Ash, MK, Bhimalli, PP, Al-Harthi, L, Sha, BE, Schneider, JR & Kelleher, NL 2022, 'Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire', Journal of Proteome Research, vol. 21, no. 1, pp. 274-288. https://doi.org/10.1021/acs.jproteome.1c00882

TY - JOUR

T1 - Next-Generation Serology by Mass Spectrometry

T2 - Readout of the SARS-CoV-2 Antibody Repertoire

AU - Melani, Rafael D.

AU - Des Soye, Benjamin J.

AU - Kafader, Jared O.

AU - Forte, Eleonora

AU - Hollas, Michael

AU - Blagojevic, Voislav

AU - Negrão, Fernanda

AU - McGee, John P.

AU - Drown, Bryon

AU - Lloyd-Jones, Cameron

AU - Seckler, Henrique S.

AU - Camarillo, Jeannie M.

AU - Compton, Philip D.

AU - LeDuc, Richard D.

AU - Early, Bryan

AU - Fellers, Ryan T.

AU - Cho, Byoung Kyu

AU - Mattamana, Basil Baby

AU - Goo, Young Ah

AU - Thomas, Paul M.

AU - Ash, Michelle K.

AU - Bhimalli, Pavan P.

AU - Al-Harthi, Lena

AU - Sha, Beverly E.

AU - Schneider, Jeffrey R.

AU - Kelleher, Neil L.

N1 - Funding Information: RBD was expressed by the Northwestern Recombinant Protein Production Core Facility. The reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Vector pCAGGS Containing the SARS-Related Coronavirus 2, Wuhan-Hu-1 Spike Glycoprotein Receptor-Binding Domain (RBD), NR-52309. IgG glycosylation and bottom-up proteomics were measured by the Northwestern Proteomics Core Facility. This study was funded by the National Institute of Health under a grant from the National Institute of General Medical Sciences P41 GM108569 (N.L.K.); the Research Corporation (Grant no. 27372, N.L.K. and E.F.); Administrative Supplement to SBIR grant number R44 GM121130 (P.D.C.); Walder Foundation grant number SCI16 (J.R.S.); the NIH Office of Director award S10 OD025194 (P.D.C.); the Northwestern Medicine Dr. Michael M. Abecassis Transplant Innovation Endowment Grant; NCI CCSG P30 CA060553 (awarded to the Robert H. Lurie Comprehensive Cancer Center). National Cancer Institute grant 1F32CA246894-01A1 (B.D.); The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: © 2021 American Chemical Society

PY - 2022/1/7

Y1 - 2022/1/7

N2 - Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We applied Ig-MS to plasma from subjects with severe and mild COVID-19 and immunized subjects after two vaccine doses, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, that could use other antigens of interest to gauge immune responses to vaccination, pathogens, or autoimmune disorders.

AB - Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We applied Ig-MS to plasma from subjects with severe and mild COVID-19 and immunized subjects after two vaccine doses, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, that could use other antigens of interest to gauge immune responses to vaccination, pathogens, or autoimmune disorders.

KW - COVID-19

KW - SARS-CoV-2

KW - antibodies

KW - individual ion mass spectrometry

KW - proteomics

KW - serology

KW - top-down mass spectrometry

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UR - http://www.scopus.com/inward/citedby.url?scp=85121237927&partnerID=8YFLogxK

U2 - 10.1021/acs.jproteome.1c00882

DO - 10.1021/acs.jproteome.1c00882

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AN - SCOPUS:85121237927

SN - 1535-3893

VL - 21

SP - 274

EP - 288

JO - Journal of Proteome Research

JF - Journal of Proteome Research

IS - 1

ER -

Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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