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Systems serology detects functionally distinct coronavirus antibody features in children and elderly

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Selva, KJ, van de Sandt, CE, Lemke, MM, Lee, CY, Shoffner, SK, Chua, BY, Davis, SK, Nguyen, THO, Rowntree, LC, Hensen, L, Koutsakos, M, Wong, CY, Mordant, F, Jackson, DC, Flanagan, KL, Crowe, J, Tosif, S, Neeland, MR, Sutton, P, Licciardi, PV, Crawford, NW, Cheng, AC, Doolan, DL, Amanat, F, Krammer, F, Chappell, K, Modhiran, N, Watterson, D, Young, P, Lee, WS, Wines, BD, Hogarth, PM, Esterbauer, R, Kelly, HG, Tan, HX, Juno, JA, Wheatley, AK, Kent, SJ, Arnold, KB, Kedzierska, K and Chung, AW 2021 , 'Systems serology detects functionally distinct coronavirus antibody features in children and elderly' , Nature Communications, vol. 12, no. 1 , doi: 10.1038/s41467-021-22236-7.

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Abstract

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.

Item Type: Article
Authors/Creators:Selva, KJ and van de Sandt, CE and Lemke, MM and Lee, CY and Shoffner, SK and Chua, BY and Davis, SK and Nguyen, THO and Rowntree, LC and Hensen, L and Koutsakos, M and Wong, CY and Mordant, F and Jackson, DC and Flanagan, KL and Crowe, J and Tosif, S and Neeland, MR and Sutton, P and Licciardi, PV and Crawford, NW and Cheng, AC and Doolan, DL and Amanat, F and Krammer, F and Chappell, K and Modhiran, N and Watterson, D and Young, P and Lee, WS and Wines, BD and Hogarth, PM and Esterbauer, R and Kelly, HG and Tan, HX and Juno, JA and Wheatley, AK and Kent, SJ and Arnold, KB and Kedzierska, K and Chung, AW
Journal or Publication Title: Nature Communications
Publisher: Nature Pub. Group
ISSN: 2041-1723
DOI / ID Number: 10.1038/s41467-021-22236-7
Copyright Information:

Copyright 2021 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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