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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 E ; Jossi, Sian E ; Perez-Toledo, Marisol ; Shields, Adrian M ; Allen, Joel D ; Watanabe, Yasunori ; Newby, Maddy L ; Cook, Alex ; Willcox, Carrie R ; Salim, Mahboob ... show 10 more
Faustini, Sian E
Jossi, Sian E
Perez-Toledo, Marisol
Shields, Adrian M
Allen, Joel D
Watanabe, Yasunori
Newby, Maddy L
Cook, Alex
Willcox, Carrie R
Salim, Mahboob
Authors
Faustini, Sian E
Jossi, Sian E
Perez-Toledo, Marisol
Shields, Adrian M
Allen, Joel D
Watanabe, Yasunori
Newby, Maddy L
Cook, Alex
Willcox, Carrie R
Salim, Mahboob
Goodall, Margaret
Heaney, Jennifer L
Marcial-Juarez, Edith
Morley, Gabriella L
Torlinska, Barbara
Wraith, David C
Veenith, Tonny
Harding, Stephen
Jolles, Stephen
Ponsford, Mark J
Plant, Tim
Huissoon, Aarnoud
O'Shea, Matthew K
Willcox, Benjamin E
Drayson, Mark T
Crispin, Max
Cunningham, Adam F
Richter, Alex G
Jossi, Sian E
Perez-Toledo, Marisol
Shields, Adrian M
Allen, Joel D
Watanabe, Yasunori
Newby, Maddy L
Cook, Alex
Willcox, Carrie R
Salim, Mahboob
Goodall, Margaret
Heaney, Jennifer L
Marcial-Juarez, Edith
Morley, Gabriella L
Torlinska, Barbara
Wraith, David C
Veenith, Tonny
Harding, Stephen
Jolles, Stephen
Ponsford, Mark J
Plant, Tim
Huissoon, Aarnoud
O'Shea, Matthew K
Willcox, Benjamin E
Drayson, Mark T
Crispin, Max
Cunningham, Adam F
Richter, Alex G
Editors
Other contributors
Affiliation
Epub Date
Issue Date
2021-05-24
Submitted date
Subjects
Alternative
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.
Citation
Faustini, S.E., Jossi, S.E., Perez-Toledo, M., Shields, A.M., Allen, J.D., Watanabe, Y., Newby, M.L., Cook, A., Willcox, C.R., Salim, M., Goodall, M., Heaney, J.L., Marcial-Juarez, E., Morley, G.L., Torlinska, B., Wraith, D.C., Veenith, T.V., Harding, S., Jolles, S., Ponsford, M.J., Plant, T., Huissoon, A., O'Shea, M.K., Willcox, B.E., Drayson, M.T., Crispin, M., Cunningham, A.F. and Richter, A.G. (2021), Development of a high-sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS-CoV-2 spike glycoprotein in serum and saliva. Immunology, 164: 135-147. https://doi.org/10.1111/imm.13349
Publisher
Journal
Research Unit
PubMed ID
33932228 (pubmed)
PubMed Central ID
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Type
Journal article
Language
en
Description
© 2021 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/imm.13349
Series/Report no.
ISSN
0019-2805
EISSN
1365-2567
ISBN
ISMN
Gov't Doc #
Sponsors
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.
Rights
Licence for published version: Creative Commons Attribution 4.0 International