期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22236-7
关键词
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资金
- Jack Ma Foundation
- Clifford Craig Foundation
- NHMRC Leadership Investigator Grant [1173871]
- NHMRC Program [1132975, 1071916, 1149990]
- Research Grants Council of the Hong Kong Special Administrative Region, China [T11-712/19-N]
- MRFF [2005544]
- Emergent Ventures Fast Grant
- NHMRC [1140509, 1102792, 1137285, 1136322]
- European Union [792532]
- Melbourne International Research Scholarship (MIRS)
- Melbourne International Fee Remission Scholarship (MIFRS) from the University of Melbourne
- NHMRC Early Career Fellowship (ECF) [APP1123673]
- NHMRC CDF2 Fellowship [1146198]
- DHB Foundation Fellowship
- Victorian Government's Medical Research Operational Infrastructure Support Program
- Marie Curie Actions (MSCA) [792532] Funding Source: Marie Curie Actions (MSCA)
- National Health and Medical Research Council of Australia [1137285, 1136322, 1146198, 1140509, 1102792, 1173871] Funding Source: NHMRC
The study reveals that elderly individuals have higher levels of cross-reactive antibodies before the COVID-19 pandemic, while children have fewer exposures to coronaviruses before the emergence of the virus, resulting in less-experienced but stronger humoral immunity. Age-dependent analysis in COVID-19 patients shows elevated class-switched antibodies in the elderly and stronger Fc responses in children.
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 Fc gamma receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fc gamma 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. Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.
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