Structurally and functionally distinct early antibody responses predict COVID-19 disease trajectory and mRNA vaccine response
Open Access
- 25 May 2021
- preprint content
- research article
- Published by Cold Spring Harbor Laboratory
Abstract
A damaging inflammatory response is strongly implicated in the pathogenesis of severe COVID-19 but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated, anti-SARS-CoV-2 IgG predicted progression from mild, to more severe COVID-19. In contrast to the antibody structures that predicted disease progression, antibodies that were elicited by mRNA SARS-CoV-2 vaccines were low in Fc afucosylation and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. To study the biology afucosylated IgG immune complexes, we developed an in vivo model which revealed that human IgG-FcγR interactions can regulate inflammation in the lung. Afucosylated IgG immune complexes induced inflammatory cytokine production and robust infiltration of the lung by immune cells. By contrast, vaccine elicited IgG did not promote an inflammatory lung response. Here, we show that IgG-FcγR interactions can regulate inflammation in the lung and define distinct lung activities associated with the IgG that predict severe COVID-19 and protection against SARS-CoV-2.One Sentence Summary: Divergent early antibody responses predict COVID-19 disease trajectory and mRNA vaccine response and are functionally distinct in vivo.Keywords
This publication has 34 references indexed in Scilit:
- Human Blood Monocyte SubsetsArteriosclerosis, Thrombosis, and Vascular Biology, 2017
- Regulation of autoantibody activity by the IL-23–TH17 axis determines the onset of autoimmune diseaseNature Immunology, 2016
- Chemokine CXCL1-Mediated Neutrophil Trafficking in the Lung: Role of CXCR2 ActivationJournal of Innate Immunity, 2015
- Anti-HA Glycoforms Drive B Cell Affinity Selection and Determine Influenza Vaccine EfficacyCell, 2015
- Loci Associated with N-Glycosylation of Human Immunoglobulin G Show Pleiotropy with Autoimmune Diseases and Haematological CancersPLoS Genetics, 2013
- Mouse model recapitulating human Fcγ receptor structural and functional diversityProceedings of the National Academy of Sciences of the United States of America, 2012
- Fc-Glycosylation of IgG1 is Modulated by B-cell StimuliMolecular & Cellular Proteomics, 2011
- Genomics Meets Glycomics—The First GWAS Study of Human N-Glycome Identifies HNF1α as a Master Regulator of Plasma Protein FucosylationPLoS Genetics, 2010
- Nomenclature of monocytes and dendritic cells in bloodBlood, 2010
- Lack of Fucose on Human IgG1 N-Linked Oligosaccharide Improves Binding to Human FcγRIII and Antibody-dependent Cellular ToxicityOnline Journal of Public Health Informatics, 2002