Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

UK COVIDsortium Investigators

doi:10.1016/j.crmeth.2022.100279

Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

UK COVIDsortium Investigators

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

2 Citations (Scopus)

Abstract

Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.

Original language	English
Article number	100279
Journal	Cell Reports Methods
Volume	2
Issue number	9
DOIs	https://doi.org/10.1016/j.crmeth.2022.100279
Publication status	Published - 19 Sept 2022

Bibliographical note

Funding Information:
The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, UKRI, or the Department of Health. We wish to thank Drs. Mike Morris and Don Cooper at Waters for their advice and consumables support. We would also like to thank Dr. Rachel Carling for her advice on the clinical translation adaption of the assay and to the members of the COVIDsortium (see supplemental information). Funding: this work was (partly) funded by the NIHR GOSH BRC, TMSRG UCL, and The Peto Foundation. R.J.B. D.M.A. and A.M.K. are supported by UKRI (MR/W020610/1). R.J.B. D.M.A. K.M. W.H. and T.B. are supported by Innovate UK (SBRI 10008614), Conceptualization, K.M.; methodology, K.G. and W.H.; formal analysis, I.D. W.H. and T.B.; investigation, I.D. J.S. J.M.G. C.P. R.J.B. T.T. C.M. G.C. M.F. and A.S.; resources, K.G. C.J.R. R.J.B. T.T. C.M. J.C.M. G.C. M.F. and T.B.; data curation, R.J.B. T.T. C.M. G.C. and M.F.; writing – original draft, W.H.; writing – review & editing, M.N. A.M.K. R.J.B. D.M.A. M.K.M. and J.C.M.; supervision, W.H. K.M. and J.C.M.; funding acquisition, J.C.M. K.M. R.J.B. and D.M.A. The authors have submitted an intellectual property claim for using the technology for clinical applications.

Funding Information:
The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, UKRI, or the Department of Health. We wish to thank Drs. Mike Morris and Don Cooper at Waters for their advice and consumables support. We would also like to thank Dr. Rachel Carling for her advice on the clinical translation adaption of the assay and to the members of the COVIDsortium (see supplemental information ). Funding: this work was (partly) funded by the NIHR GOSH BRC , TMSRG UCL , and The Peto Foundation . R.J.B., D.M.A., and A.M.K. are supported by UKRI ( MR / W020610/1 ). R.J.B., D.M.A., K.M., W.H., and T.B. are supported by Innovate UK ( SBRI 10008614 )

Publisher Copyright:
© 2022 The Author(s)

Keywords

COVID-19
SARS-CoV-2
complement: immunoglobulin
delta variant
mass spectrometry
omicron variant
proteomics
vaccination
variant of concern

UN SDGs

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

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10.1016/j.crmeth.2022.100279

Cite this

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title = "Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response",

abstract = "Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.",

keywords = "COVID-19, SARS-CoV-2, complement: immunoglobulin, delta variant, mass spectrometry, omicron variant, proteomics, vaccination, variant of concern",

author = "{UK COVIDsortium Investigators} and Ivan Doykov and Tomas Baldwin and Justyna Spiewak and Gilmour, {Kimberly C.} and Gibbons, {Joseph M.} and Corinna Pade and Reynolds, {Catherine J.} and {{\'A}ine McKnight}, McKnight and Mahdad Noursadeghi and Maini, {Mala K.} and Charlotte Manisty and Thomas Treibel and Gabriella Captur and Marianna Fontana and Boyton, {Rosemary J.} and Altmann, {Daniel M.} and Tim Brooks and Amanda Semper and Hakam Abbass and Aderonke Abiodun and Mashael Alfarih and Zoe Alldis and Amin, {Oliver E.} and Mervyn Andiapen and Jessica Artico and Augusto, {Jo{\~a}o B.} and Baca, {Georgina L.} and Bailey, {Sasha N.L.} and Bhuva, {Anish N.} and Alex Boulter and Ruth Bowles and Bracken, {Olivia V.} and Ben O'Brien and Natalie Bullock and Butler, {David K.} and Olivia Carr and Nicola Champion and Carmen Chan and Aneesh Chandran and Tom Coleman and {Couto de Sousa}, Jorge and Xose Couto-Parada and Eleanor Cross and Teresa Cutino-Moguel and Silvia D'Arcangelo and Jacqueline Hewson and Jessica Jones and Christopher Moon and Ashley Otter and Cathy Rowe",

note = "Funding Information: The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, UKRI, or the Department of Health. We wish to thank Drs. Mike Morris and Don Cooper at Waters for their advice and consumables support. We would also like to thank Dr. Rachel Carling for her advice on the clinical translation adaption of the assay and to the members of the COVIDsortium (see supplemental information). Funding: this work was (partly) funded by the NIHR GOSH BRC, TMSRG UCL, and The Peto Foundation. R.J.B. D.M.A. and A.M.K. are supported by UKRI (MR/W020610/1). R.J.B. D.M.A. K.M. W.H. and T.B. are supported by Innovate UK (SBRI 10008614), Conceptualization, K.M.; methodology, K.G. and W.H.; formal analysis, I.D. W.H. and T.B.; investigation, I.D. J.S. J.M.G. C.P. R.J.B. T.T. C.M. G.C. M.F. and A.S.; resources, K.G. C.J.R. R.J.B. T.T. C.M. J.C.M. G.C. M.F. and T.B.; data curation, R.J.B. T.T. C.M. G.C. and M.F.; writing – original draft, W.H.; writing – review & editing, M.N. A.M.K. R.J.B. D.M.A. M.K.M. and J.C.M.; supervision, W.H. K.M. and J.C.M.; funding acquisition, J.C.M. K.M. R.J.B. and D.M.A. The authors have submitted an intellectual property claim for using the technology for clinical applications. Funding Information: The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, UKRI, or the Department of Health. We wish to thank Drs. Mike Morris and Don Cooper at Waters for their advice and consumables support. We would also like to thank Dr. Rachel Carling for her advice on the clinical translation adaption of the assay and to the members of the COVIDsortium (see supplemental information ). Funding: this work was (partly) funded by the NIHR GOSH BRC , TMSRG UCL , and The Peto Foundation . R.J.B., D.M.A., and A.M.K. are supported by UKRI ( MR / W020610/1 ). R.J.B., D.M.A., K.M., W.H., and T.B. are supported by Innovate UK ( SBRI 10008614 ) Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = sep,

day = "19",

doi = "10.1016/j.crmeth.2022.100279",

language = "English",

volume = "2",

journal = "Cell Reports Methods",

issn = "2667-2375",

publisher = "Cell Press",

number = "9",

}

TY - JOUR

T1 - Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

AU - UK COVIDsortium Investigators

AU - Doykov, Ivan

AU - Baldwin, Tomas

AU - Spiewak, Justyna

AU - Gilmour, Kimberly C.

AU - Gibbons, Joseph M.

AU - Pade, Corinna

AU - Reynolds, Catherine J.

AU - Áine McKnight, McKnight

AU - Noursadeghi, Mahdad

AU - Maini, Mala K.

AU - Manisty, Charlotte

AU - Treibel, Thomas

AU - Captur, Gabriella

AU - Fontana, Marianna

AU - Boyton, Rosemary J.

AU - Altmann, Daniel M.

AU - Brooks, Tim

AU - Semper, Amanda

AU - Abbass, Hakam

AU - Abiodun, Aderonke

AU - Alfarih, Mashael

AU - Alldis, Zoe

AU - Amin, Oliver E.

AU - Andiapen, Mervyn

AU - Artico, Jessica

AU - Augusto, João B.

AU - Baca, Georgina L.

AU - Bailey, Sasha N.L.

AU - Bhuva, Anish N.

AU - Boulter, Alex

AU - Bowles, Ruth

AU - Bracken, Olivia V.

AU - O'Brien, Ben

AU - Bullock, Natalie

AU - Butler, David K.

AU - Carr, Olivia

AU - Champion, Nicola

AU - Chan, Carmen

AU - Chandran, Aneesh

AU - Coleman, Tom

AU - Couto de Sousa, Jorge

AU - Couto-Parada, Xose

AU - Cross, Eleanor

AU - Cutino-Moguel, Teresa

AU - D'Arcangelo, Silvia

AU - Hewson, Jacqueline

AU - Jones, Jessica

AU - Moon, Christopher

AU - Otter, Ashley

AU - Rowe, Cathy

N1 - Funding Information: The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, UKRI, or the Department of Health. We wish to thank Drs. Mike Morris and Don Cooper at Waters for their advice and consumables support. We would also like to thank Dr. Rachel Carling for her advice on the clinical translation adaption of the assay and to the members of the COVIDsortium (see supplemental information). Funding: this work was (partly) funded by the NIHR GOSH BRC, TMSRG UCL, and The Peto Foundation. R.J.B. D.M.A. and A.M.K. are supported by UKRI (MR/W020610/1). R.J.B. D.M.A. K.M. W.H. and T.B. are supported by Innovate UK (SBRI 10008614), Conceptualization, K.M.; methodology, K.G. and W.H.; formal analysis, I.D. W.H. and T.B.; investigation, I.D. J.S. J.M.G. C.P. R.J.B. T.T. C.M. G.C. M.F. and A.S.; resources, K.G. C.J.R. R.J.B. T.T. C.M. J.C.M. G.C. M.F. and T.B.; data curation, R.J.B. T.T. C.M. G.C. and M.F.; writing – original draft, W.H.; writing – review & editing, M.N. A.M.K. R.J.B. D.M.A. M.K.M. and J.C.M.; supervision, W.H. K.M. and J.C.M.; funding acquisition, J.C.M. K.M. R.J.B. and D.M.A. The authors have submitted an intellectual property claim for using the technology for clinical applications. Funding Information: The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, UKRI, or the Department of Health. We wish to thank Drs. Mike Morris and Don Cooper at Waters for their advice and consumables support. We would also like to thank Dr. Rachel Carling for her advice on the clinical translation adaption of the assay and to the members of the COVIDsortium (see supplemental information ). Funding: this work was (partly) funded by the NIHR GOSH BRC , TMSRG UCL , and The Peto Foundation . R.J.B., D.M.A., and A.M.K. are supported by UKRI ( MR / W020610/1 ). R.J.B., D.M.A., K.M., W.H., and T.B. are supported by Innovate UK ( SBRI 10008614 ) Publisher Copyright: © 2022 The Author(s)

PY - 2022/9/19

Y1 - 2022/9/19

N2 - Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.

AB - Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.

KW - COVID-19

KW - SARS-CoV-2

KW - complement: immunoglobulin

KW - delta variant

KW - mass spectrometry

KW - omicron variant

KW - proteomics

KW - vaccination

KW - variant of concern

UR - http://www.scopus.com/inward/record.url?scp=85136698547&partnerID=8YFLogxK

U2 - 10.1016/j.crmeth.2022.100279

DO - 10.1016/j.crmeth.2022.100279

M3 - Article

AN - SCOPUS:85136698547

SN - 2667-2375

VL - 2

JO - Cell Reports Methods

JF - Cell Reports Methods

IS - 9

M1 - 100279

ER -

Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Abstract

Bibliographical note

Keywords

UN SDGs

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