Cell Reports: Methods (Sep 2022)
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,
- James C. Moon,
- Kevin Mills,
- Wendy E. Heywood,
- Hakam Abbass,
- Aderonke Abiodun,
- Mashael Alfarih,
- Zoe Alldis,
- Daniel M. Altmann,
- Oliver E. Amin,
- Mervyn Andiapen,
- Jessica Artico,
- João B. Augusto,
- Georgina L. Baca,
- Sasha N.L. Bailey,
- Anish N. Bhuva,
- Alex Boulter,
- Ruth Bowles,
- Rosemary J. Boyton,
- Olivia V. Bracken,
- Ben O’Brien,
- Tim Brooks,
- Natalie Bullock,
- David K. Butler,
- Gabriella Captur,
- Olivia Carr,
- Nicola Champion,
- Carmen Chan,
- Aneesh Chandran,
- Tom Coleman,
- Jorge Couto de Sousa,
- Xose Couto-Parada,
- Eleanor Cross,
- Teresa Cutino-Moguel,
- Silvia D’Arcangelo,
- Rhodri H. Davies,
- Brooke Douglas,
- Cecilia Di Genova,
- Keenan Dieobi-Anene,
- Mariana O. Diniz,
- Anaya Ellis,
- Karen Feehan,
- Malcolm Finlay,
- Marianna Fontana,
- Nasim Forooghi,
- Sasha Francis,
- Joseph M. Gibbons,
- David Gillespie,
- Derek Gilroy,
- Matt Hamblin,
- Gabrielle Harker,
- Georgia Hemingway,
- Jacqueline Hewson,
- Wendy Heywood,
- Lauren M. Hickling,
- Bethany Hicks,
- Aroon D. Hingorani,
- Lee Howes,
- Ivie Itua,
- Victor Jardim,
- Wing-Yiu Jason Lee,
- Melaniepetra Jensen,
- Jessica Jones,
- Meleri Jones,
- George Joy,
- Vikas Kapil,
- Caoimhe Kelly,
- Hibba Kurdi,
- Jonathan Lambourne,
- Kai-Min Lin,
- Siyi Liu,
- Aaron Lloyd,
- Sarah Louth,
- Mala K. Maini,
- Vineela Mandadapu,
- Charlotte Manisty,
- Áine McKnight,
- Katia Menacho,
- Celina Mfuko,
- Kevin Mills,
- Sebastian Millward,
- Oliver Mitchelmore,
- Christopher Moon,
- James Moon,
- Diana Muñoz Sandoval,
- Sam M. Murray,
- Mahdad Noursadeghi,
- Ashley Otter,
- Corinna Pade,
- Susana Palma,
- Ruth Parker,
- Kush Patel,
- Mihaela Pawarova,
- Steffen E. Petersen,
- Brian Piniera,
- Franziska P. Pieper,
- Lisa Rannigan,
- Alicja Rapala,
- Catherine J. Reynolds,
- Amy Richards,
- Matthew Robathan,
- Joshua Rosenheim,
- Cathy Rowe,
- Matthew Royds,
- Jane Sackville West,
- Genine Sambile,
- Nathalie M. Schmidt,
- Hannah Selman,
- Amanda Semper,
- Andreas Seraphim,
- Mihaela Simion,
- Angelique Smit,
- Michelle Sugimoto,
- Leo Swadling,
- Stephen Taylor,
- Nigel Temperton,
- Stephen Thomas,
- George D. Thornton,
- Thomas A. Treibel,
- Art Tucker,
- Ann Varghese,
- Jessry Veerapen,
- Mohit Vijayakumar,
- Tim Warner,
- Sophie Welch,
- Hannah White,
- Theresa Wodehouse,
- Lucinda Wynne,
- Dan Zahedi
Affiliations
- Ivan Doykov
- Translational Mass Spectrometry Research Group, Genetics & Genomic Medicine Department, UCL Institute of Child Health, London, UK; Great Ormond Street Biomedical Research Centre, UCL Institute of Child Health London
- Tomas Baldwin
- Translational Mass Spectrometry Research Group, Genetics & Genomic Medicine Department, UCL Institute of Child Health, London, UK
- Justyna Spiewak
- Translational Mass Spectrometry Research Group, Genetics & Genomic Medicine Department, UCL Institute of Child Health, London, UK
- Kimberly C. Gilmour
- Great Ormond Street Children’s Hospital NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK
- Joseph M. Gibbons
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Corinna Pade
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Catherine J. Reynolds
- Department of Infectious Disease, Imperial College London, London, UK
- Áine McKnight
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Mahdad Noursadeghi
- Division of Infection and Immunity, University College London, London, UK
- Mala K. Maini
- Division of Infection and Immunity, University College London, London, UK
- Charlotte Manisty
- St. Bartholomew’s Hospital, Barts Health NHS Trust, London, UK; Institute of Cardiovascular Science, University College London, London, UK
- Thomas Treibel
- St. Bartholomew’s Hospital, Barts Health NHS Trust, London, UK; Institute of Cardiovascular Science, University College London, London, UK
- Gabriella Captur
- Institute of Cardiovascular Science, University College London, London, UK; Royal Free London NHS Foundation Trust, Pond Street, London NW3 2QG, UK
- Marianna Fontana
- Institute of Cardiovascular Science, University College London, London, UK; Royal Free London NHS Foundation Trust, Pond Street, London NW3 2QG, UK
- Rosemary J. Boyton
- Department of Infectious Disease, Imperial College London, London, UK; Lung Division, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
- Daniel M. Altmann
- Department of Immunology and Inflammation, Imperial College London, London, UK
- Tim Brooks
- UK Health Security Agency, Porton Down, UK
- Amanda Semper
- UK Health Security Agency, Porton Down, UK
- James C. Moon
- St. Bartholomew’s Hospital, Barts Health NHS Trust, London, UK; Institute of Cardiovascular Science, University College London, London, UK
- Kevin Mills
- Translational Mass Spectrometry Research Group, Genetics & Genomic Medicine Department, UCL Institute of Child Health, London, UK; Great Ormond Street Biomedical Research Centre, UCL Institute of Child Health London
- Wendy E. Heywood
- Translational Mass Spectrometry Research Group, Genetics & Genomic Medicine Department, UCL Institute of Child Health, London, UK; Great Ormond Street Biomedical Research Centre, UCL Institute of Child Health London; Corresponding author
- Hakam Abbass
- Aderonke Abiodun
- Mashael Alfarih
- Zoe Alldis
- Daniel M. Altmann
- Oliver E. Amin
- Mervyn Andiapen
- Jessica Artico
- João B. Augusto
- Georgina L. Baca
- Sasha N.L. Bailey
- Anish N. Bhuva
- Alex Boulter
- Ruth Bowles
- Rosemary J. Boyton
- Olivia V. Bracken
- Ben O’Brien
- Tim Brooks
- Natalie Bullock
- David K. Butler
- Gabriella Captur
- Olivia Carr
- Nicola Champion
- Carmen Chan
- Aneesh Chandran
- Tom Coleman
- Jorge Couto de Sousa
- Xose Couto-Parada
- Eleanor Cross
- Teresa Cutino-Moguel
- Silvia D’Arcangelo
- Rhodri H. Davies
- Brooke Douglas
- Cecilia Di Genova
- Keenan Dieobi-Anene
- Mariana O. Diniz
- Anaya Ellis
- Karen Feehan
- Malcolm Finlay
- Marianna Fontana
- Nasim Forooghi
- Sasha Francis
- Joseph M. Gibbons
- David Gillespie
- Derek Gilroy
- Matt Hamblin
- Gabrielle Harker
- Georgia Hemingway
- Jacqueline Hewson
- Wendy Heywood
- Lauren M. Hickling
- Bethany Hicks
- Aroon D. Hingorani
- Lee Howes
- Ivie Itua
- Victor Jardim
- Wing-Yiu Jason Lee
- Melaniepetra Jensen
- Jessica Jones
- Meleri Jones
- George Joy
- Vikas Kapil
- Caoimhe Kelly
- Hibba Kurdi
- Jonathan Lambourne
- Kai-Min Lin
- Siyi Liu
- Aaron Lloyd
- Sarah Louth
- Mala K. Maini
- Vineela Mandadapu
- Charlotte Manisty
- Áine McKnight
- Katia Menacho
- Celina Mfuko
- Kevin Mills
- Sebastian Millward
- Oliver Mitchelmore
- Christopher Moon
- James Moon
- Diana Muñoz Sandoval
- Sam M. Murray
- Mahdad Noursadeghi
- Ashley Otter
- Corinna Pade
- Susana Palma
- Ruth Parker
- Kush Patel
- Mihaela Pawarova
- Steffen E. Petersen
- Brian Piniera
- Franziska P. Pieper
- Lisa Rannigan
- Alicja Rapala
- Catherine J. Reynolds
- Amy Richards
- Matthew Robathan
- Joshua Rosenheim
- Cathy Rowe
- Matthew Royds
- Jane Sackville West
- Genine Sambile
- Nathalie M. Schmidt
- Hannah Selman
- Amanda Semper
- Andreas Seraphim
- Mihaela Simion
- Angelique Smit
- Michelle Sugimoto
- Leo Swadling
- Stephen Taylor
- Nigel Temperton
- Stephen Thomas
- George D. Thornton
- Thomas A. Treibel
- Art Tucker
- Ann Varghese
- Jessry Veerapen
- Mohit Vijayakumar
- Tim Warner
- Sophie Welch
- Hannah White
- Theresa Wodehouse
- Lucinda Wynne
- Dan Zahedi
- Journal volume & issue
-
Vol. 2,
no. 9
p. 100279
Abstract
Summary: 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. Motivation: Assays for measuring serum antibody responses are typically limited to measurement of a total or single immunoglobulin isotype. The antibody response is far more complex, with multiple immunoglobulin classes, isotypes, and complement factors involved. This is a potential wealth of information that is typically understudied and missed by existing tests. The global COVID-19 pandemic has highlighted the need to understand better the immune response in respect to vaccine development and emerging new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants. Using the ability of tandem mass spectrometry to multiplex and directly and accurately measure the antibody complex, we devised an alternative assay to capture this valuable information.
