Heterologous Immune Responses of Serum IgG and Secretory IgA Against the Spike Protein of Endemic Coronaviruses During Severe COVID-19

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Mar 31

PMID 35355988

Authors

Wouter L Smit

Sophie van Tol

Sanne van der Wal

Femke van Vulpen

Shannon la Grouw

Lenneke van Lelyveld

Gijs Limonard

Ailko Bossink

Gert-Jan Godeke

Sandhya Shrestha

Johan Reimerink

Dirk Eggink

Chantal Reusken

Michiel Heron

Steven Thijsen

Affiliations

Soon will be listed here.

Abstract

Defining immune correlates of disease severity is important to better understand the immunopathogenesis in COVID-19. Here we made use of a protein microarray platform to detect IgG- and IgA-reactive antibodies in sera and saliva respectively, and assess cross-reactivity between SARS-CoV-2 and endemic coronaviruses (eCoVs). IgG responses against the full protein of spike, but not the S1 subunit, were significantly higher in convalescent sera of patients with severe disease compared to mild disease and healthy controls. In addition, we detected reactivity of secretory IgA to eCoVs in saliva of patients with severe disease, not present in patients with moderate disease or seropositive healthy controls. These heterologous immune responses are in line with non-protective cross-reactivity, and support a potential role for immune imprinting in the pathogenesis of severe COVID-19.

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References

Welsh R, Fujinami R . Pathogenic epitopes, heterologous immunity and vaccine design. Nat Rev Microbiol. 2007; 5(7):555-63. PMC: 7097378. DOI: 10.1038/nrmicro1709. View

Cueno M, Imai K . Structural Insights on the SARS-CoV-2 Variants of Concern Spike Glycoprotein: A Computational Study With Possible Clinical Implications. Front Genet. 2021; 12:773726. PMC: 8568765. DOI: 10.3389/fgene.2021.773726. View

Lucas C, Klein J, Sundaram M, Liu F, Wong P, Silva J . Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nat Med. 2021; 27(7):1178-1186. PMC: 8785364. DOI: 10.1038/s41591-021-01355-0. View

Edridge A, Kaczorowska J, Hoste A, Bakker M, Klein M, Loens K . Seasonal coronavirus protective immunity is short-lasting. Nat Med. 2020; 26(11):1691-1693. DOI: 10.1038/s41591-020-1083-1. View

Lv H, Wu N, Tsang O, Yuan M, Perera R, Leung W . Cross-reactive Antibody Response between SARS-CoV-2 and SARS-CoV Infections. Cell Rep. 2020; 31(9):107725. PMC: 7231734. DOI: 10.1016/j.celrep.2020.107725. View

Grobben M, van der Straten K, Brouwer P, Brinkkemper M, Maisonnasse P, Dereuddre-Bosquet N . Cross-reactive antibodies after SARS-CoV-2 infection and vaccination. Elife. 2021; 10. PMC: 8610423. DOI: 10.7554/eLife.70330. View

Aguilar-Bretones M, Westerhuis B, Raadsen M, de Bruin E, Chandler F, Okba N . Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19. J Clin Invest. 2021; 131(21). PMC: 8553556. DOI: 10.1172/JCI150613. View

Mateus J, Grifoni A, Tarke A, Sidney J, Ramirez S, Dan J . Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. 2020; 370(6512):89-94. PMC: 7574914. DOI: 10.1126/science.abd3871. View

Kobayashi H, Song C, Ikei H, Park B, Kagawa T, Miyazaki Y . Diurnal Changes in Distribution Characteristics of Salivary Cortisol and Immunoglobulin A Concentrations. Int J Environ Res Public Health. 2017; 14(9). PMC: 5615524. DOI: 10.3390/ijerph14090987. View

10.

Hicks J, Klumpp-Thomas C, Kalish H, Shunmugavel A, Mehalko J, Denson J . Serologic Cross-Reactivity of SARS-CoV-2 with Endemic and Seasonal Betacoronaviruses. J Clin Immunol. 2021; 41(5):906-913. PMC: 7962425. DOI: 10.1007/s10875-021-00997-6. View

11.

McNaughton A, Paton R, Edmans M, Youngs J, Wellens J, Phalora P . Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses. JCI Insight. 2022; 7(13). PMC: 9310533. DOI: 10.1172/jci.insight.156372. View

12.

Bates T, Weinstein J, Farley S, Leier H, Messer W, Tafesse F . Cross-reactivity of SARS-CoV structural protein antibodies against SARS-CoV-2. Cell Rep. 2021; 34(7):108737. PMC: 7835103. DOI: 10.1016/j.celrep.2021.108737. View

13.

Anderson E, Goodwin E, Verma A, Arevalo C, Bolton M, Weirick M . Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection. Cell. 2021; 184(7):1858-1864.e10. PMC: 7871851. DOI: 10.1016/j.cell.2021.02.010. View

14.

Fung T, Liu D . Human Coronavirus: Host-Pathogen Interaction. Annu Rev Microbiol. 2019; 73:529-557. DOI: 10.1146/annurev-micro-020518-115759. View

15.

Chow E . The Multisystem Inflammatory Syndrome in Adults With SARS-CoV-2 Infection-Another Piece of an Expanding Puzzle. JAMA Netw Open. 2021; 4(5):e2110344. DOI: 10.1001/jamanetworkopen.2021.10344. View

16.

Dessie Z, Zewotir T . Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect Dis. 2021; 21(1):855. PMC: 8380115. DOI: 10.1186/s12879-021-06536-3. View

17.

Liu Y, Li J, Zhang F, Qin W, Yao G, He X . Molecular cloning and characterization of the human ASB-8 gene encoding a novel member of ankyrin repeat and SOCS box containing protein family. Biochem Biophys Res Commun. 2003; 300(4):972-9. DOI: 10.1016/s0006-291x(02)02971-6. View

18.

Bert N, Tan A, Kunasegaran K, Tham C, Hafezi M, Chia A . SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020; 584(7821):457-462. DOI: 10.1038/s41586-020-2550-z. View

19.

Dobano C, Jimenez A, Rubio R, Alonso S, Ramirez-Morros A, Vidal M . Spike-based COVID-19 immunization increases antibodies to nucleocapsid antigen. Transl Res. 2021; 240:26-32. PMC: 8546430. DOI: 10.1016/j.trsl.2021.10.004. View

20.

Grifoni A, Weiskopf D, Ramirez S, Mateus J, Dan J, Rydyznski Moderbacher C . Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020; 181(7):1489-1501.e15. PMC: 7237901. DOI: 10.1016/j.cell.2020.05.015. View