Development of a high-sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS-CoV-2 spike glycoprotein in serum and saliva

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Development of a high-sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS-CoV-2 spike glycoprotein in serum and saliva. / Faustini, Sian; Jossi, Sian; Perez-Toledo, Marisol; Shields, Adrian; Allen, Joel D; Watanabe, Yasunori; Newby, Maddy L; Cook, Alexander; Willcox, Carrie; Salim, Mahboob; Goodall, Margaret; Heaney, Jennifer; Marcial-Juarez, Edith; Morley, Gabriella; Torlinska, Barbara; Wraith, David; Veenith, T; Harding, Stephen; Jolles, Stephen; Mark, Ponsford J; Plant, Tim; Huissoon, Aarnoud; O’Shea, Matthew K.; Willcox, Benjamin; Drayson, Mark; Crispin, Max; Cunningham, Adam; Richter, Alex.

In: Immunology, 01.05.2021.

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Faustini, Sian ; Jossi, Sian ; Perez-Toledo, Marisol ; Shields, Adrian ; Allen, Joel D ; Watanabe, Yasunori ; Newby, Maddy L ; Cook, Alexander ; Willcox, Carrie ; Salim, Mahboob ; Goodall, Margaret ; Heaney, Jennifer ; Marcial-Juarez, Edith ; Morley, Gabriella ; Torlinska, Barbara ; Wraith, David ; Veenith, T ; Harding, Stephen ; Jolles, Stephen ; Mark, Ponsford J ; Plant, Tim ; Huissoon, Aarnoud ; O’Shea, Matthew K. ; Willcox, Benjamin ; Drayson, Mark ; Crispin, Max ; Cunningham, Adam ; Richter, Alex. / Development of a high-sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS-CoV-2 spike glycoprotein in serum and saliva. In: Immunology. 2021.

Bibtex

@article{b279beabd98448d1a7f82849374c3237,
title = "Development of a high-sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS-CoV-2 spike glycoprotein in serum and saliva",
abstract = "Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non-hospitalized SARS-CoV-2-infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT-PCR confirmed, non-hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti-spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS-CoV-2 infection.",
keywords = "COVID-19, ELISA, SARS-CoV-2, antibodies",
author = "Sian Faustini and Sian Jossi and Marisol Perez-Toledo and Adrian Shields and Allen, {Joel D} and Yasunori Watanabe and Newby, {Maddy L} and Alexander Cook and Carrie Willcox and Mahboob Salim and Margaret Goodall and Jennifer Heaney and Edith Marcial-Juarez and Gabriella Morley and Barbara Torlinska and David Wraith and T Veenith and Stephen Harding and Stephen Jolles and Mark, {Ponsford J} and Tim Plant and Aarnoud Huissoon and O{\textquoteright}Shea, {Matthew K.} and Benjamin Willcox and Mark Drayson and Max Crispin and Adam Cunningham and Alex Richter",
note = "Funding Information: AFC is grateful for funding from the Medical Research Council, the Global Challenges Research Fund (GCRF) and the Institute for Global Innovation (IGI, Project 3107) of the University of Birmingham. This study was supported by the UK National Institute for Health Research, Birmingham Biomedical Research Centres Funding scheme. The work in Prof. Max Crispin's laboratory was funded by the International AIDS Vaccine Initiative, Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (OPP1196345/INV‐008813, OPP1084519 and OPP1115782), the Scripps Consortium for HIV Vaccine Development (CHAVD) (NIH: National Institute for Allergy and Infectious Diseases AI144462) and the University of Southampton Coronavirus Response Fund. MJP is funded by the Welsh Clinical Academic Training (WCAT) programme and is a participant in the NIH Graduate Partnership Program. The CoCo study was funded internally by the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. Publisher Copyright: {\textcopyright} 2021 The Authors. Immunology published by John Wiley & Sons Ltd.",
year = "2021",
month = may,
day = "1",
doi = "10.1111/imm.13349",
language = "English",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley",

}

RIS

TY - JOUR

T1 - Development of a high-sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS-CoV-2 spike glycoprotein in serum and saliva

AU - Faustini, Sian

AU - Jossi, Sian

AU - Perez-Toledo, Marisol

AU - Shields, Adrian

AU - Allen, Joel D

AU - Watanabe, Yasunori

AU - Newby, Maddy L

AU - Cook, Alexander

AU - Willcox, Carrie

AU - Salim, Mahboob

AU - Goodall, Margaret

AU - Heaney, Jennifer

AU - Marcial-Juarez, Edith

AU - Morley, Gabriella

AU - Torlinska, Barbara

AU - Wraith, David

AU - Veenith, T

AU - Harding, Stephen

AU - Jolles, Stephen

AU - Mark, Ponsford J

AU - Plant, Tim

AU - Huissoon, Aarnoud

AU - O’Shea, Matthew K.

AU - Willcox, Benjamin

AU - Drayson, Mark

AU - Crispin, Max

AU - Cunningham, Adam

AU - Richter, Alex

N1 - Funding Information: AFC is grateful for funding from the Medical Research Council, the Global Challenges Research Fund (GCRF) and the Institute for Global Innovation (IGI, Project 3107) of the University of Birmingham. This study was supported by the UK National Institute for Health Research, Birmingham Biomedical Research Centres Funding scheme. The work in Prof. Max Crispin's laboratory was funded by the International AIDS Vaccine Initiative, Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (OPP1196345/INV‐008813, OPP1084519 and OPP1115782), the Scripps Consortium for HIV Vaccine Development (CHAVD) (NIH: National Institute for Allergy and Infectious Diseases AI144462) and the University of Southampton Coronavirus Response Fund. MJP is funded by the Welsh Clinical Academic Training (WCAT) programme and is a participant in the NIH Graduate Partnership Program. The CoCo study was funded internally by the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. Publisher Copyright: © 2021 The Authors. Immunology published by John Wiley & Sons Ltd.

PY - 2021/5/1

Y1 - 2021/5/1

N2 - Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non-hospitalized SARS-CoV-2-infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT-PCR confirmed, non-hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti-spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS-CoV-2 infection.

AB - Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non-hospitalized SARS-CoV-2-infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT-PCR confirmed, non-hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti-spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS-CoV-2 infection.

KW - COVID-19

KW - ELISA

KW - SARS-CoV-2

KW - antibodies

UR - http://www.scopus.com/inward/record.url?scp=85106229393&partnerID=8YFLogxK

U2 - 10.1111/imm.13349

DO - 10.1111/imm.13349

M3 - Article

C2 - 33932228

JO - Immunology

JF - Immunology

SN - 0019-2805

ER -