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

Ivan Doykov; Tomas Baldwin; Justyna Spiewak; Kimberly C. Gilmour; Joseph M. Gibbons; Corinna Pade; Catherine J. Reynolds; Áine McKnight; Mahdad Noursadeghi; Mala K. Maini; Charlotte Manisty; Thomas Treibel; Gabriella Captur; Marianna Fontana; Rosemary J. Boyton; Daniel M. Altmann; Tim Brooks; Amanda Semper; UK COVIDsortium Investigators; James C. Moon; Kevin Mills; Wendy E. Heywood

doi:10.1016/j.crmeth.2022.100279

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

Ivan Doykov (Lead Author), Tomas Baldwin, Justyna Spiewak, Kimberly C. Gilmour, Joseph M. Gibbons, Corinna Pade, Catherine J. Reynolds, Áine McKnight, Mahdad Noursadeghi, Mala K. Maini, Charlotte Manisty, Thomas Treibel, Gabriella Captur, Marianna Fontana, Rosemary J. Boyton, Daniel M. Altmann, Tim Brooks, Amanda Semper, UK COVIDsortium Investigators, James C. MoonKevin Mills, Wendy E. Heywood

Norwich Medical School

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

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
Early online date	12 Aug 2022
DOIs	https://doi.org/10.1016/j.crmeth.2022.100279
Publication status	Published - 19 Sept 2022

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Cite this

Doykov, I., Baldwin, T., Spiewak, J., Gilmour, K. C., Gibbons, J. M., Pade, C., Reynolds, C. J., McKnight, Á., Noursadeghi, M., Maini, M. K., Manisty, C., Treibel, T., Captur, G., Fontana, M., Boyton, R. J., Altmann, D. M., Brooks, T., Semper, A., UK COVIDsortium Investigators, ... Heywood, W. E. (2022). Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response. Cell Reports Methods, 2(9), Article 100279. https://doi.org/10.1016/j.crmeth.2022.100279

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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.",

author = "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 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 {UK COVIDsortium Investigators} and Moon, {James C.} and Kevin Mills and Heywood, {Wendy E.} and Hickling, {Lauren M.}",

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Doykov, I, Baldwin, T, Spiewak, J, Gilmour, KC, Gibbons, JM, Pade, C, Reynolds, CJ, McKnight, Á, Noursadeghi, M, Maini, MK, Manisty, C, Treibel, T, Captur, G, Fontana, M, Boyton, RJ, Altmann, DM, Brooks, T, Semper, A, UK COVIDsortium Investigators, Moon, JC, Mills, K & Heywood, WE 2022, 'Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response', Cell Reports Methods, vol. 2, no. 9, 100279. https://doi.org/10.1016/j.crmeth.2022.100279

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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 - McKnight, Áine

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 - UK COVIDsortium Investigators

AU - Moon, James C.

AU - Mills, Kevin

AU - Heywood, Wendy E.

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PY - 2022/9/19

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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.

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DO - 10.1016/j.crmeth.2022.100279

M3 - Article

SN - 2667-2375

VL - 2

JO - Cell Reports Methods

JF - Cell Reports Methods

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ER -