Bulk IgG Glycosylation Predicts COVID-19 Severity and Vaccine Antibody Response

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 Dec 9

PMID 36493786

Authors

Michelle K Ash

Pavan P Bhimalli

Byoung-Kyu Cho

Basil Baby Mattamana

Stephanie Gambut

Imad Tarhoni

Cristina L Fhied

Anjelica F Reyes

Samantha J Welninski

Jaison Arivalagan

Fernanda Negrao

Renu Goel

Todd L Beck

Thomas J Hope

Beverly E Sha

Young Ah Goo

Lena Al-Harthi

Joao I Mamede

Jeffrey A Borgia

Neil L Kelleher

Jeffrey R Schneider

Affiliations

Soon will be listed here.

Abstract

Although vaccination efforts have expanded, there are still gaps in our understanding surrounding the immune response to SARS-CoV-2. Measuring IgG Fc glycosylation provides insight into an infected individual's inflammatory state, among other functions. We set out to interrogate bulk IgG glycosylation changes from SARS-CoV-2 infection and vaccination, using plasma from mild or hospitalized COVID-19 patients, and from vaccinated individuals. Inflammatory glycans are elevated in hospitalized COVID-19 patients and increase over time, while mild patients have anti-inflammatory glycans that increase over time, including increased sialic acid correlating with RBD antibody levels. Vaccinated individuals with low RBD antibody levels and low neutralization have the same IgG glycan traits as hospitalized COVID-19 patients. In addition, a small vaccinated cohort reveals a decrease in inflammatory glycans associated with peak IgG concentrations and neutralization. This report characterizes the bulk IgG glycome associated with COVID-19 severity and vaccine responsiveness and can help guide future studies into SARS-CoV-2 protective immunity.

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References

Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H . Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020; 130(5):2620-2629. PMC: 7190990. DOI: 10.1172/JCI137244. View

Ozer E, Simons L, Adewumi O, Fowotade A, Omoruyi E, Adeniji J . Multiple expansions of globally uncommon SARS-CoV-2 lineages in Nigeria. Nat Commun. 2022; 13(1):688. PMC: 8813984. DOI: 10.1038/s41467-022-28317-5. View

Bas M, Terrier A, Jacque E, Dehenne A, Pochet-Beghin V, Beghin C . Fc Sialylation Prolongs Serum Half-Life of Therapeutic Antibodies. J Immunol. 2019; 202(5):1582-1594. DOI: 10.4049/jimmunol.1800896. View

Petrovic T, Alves I, Bugada D, Pascual J, Vuckovic F, Skelin A . Composition of the immunoglobulin G glycome associates with the severity of COVID-19. Glycobiology. 2020; 31(4):372-377. PMC: 7717252. DOI: 10.1093/glycob/cwaa102. View

Melani R, Des Soye B, Kafader J, Forte E, Hollas M, Blagojevic V . Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire. J Proteome Res. 2021; 21(1):274-288. PMC: 8673472. DOI: 10.1021/acs.jproteome.1c00882. View

Arnold J, Wormald M, Sim R, Rudd P, Dwek R . The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol. 2006; 25:21-50. DOI: 10.1146/annurev.immunol.25.022106.141702. View

Selman M, de Jong S, Soonawala D, Kroon F, Adegnika A, Deelder A . Changes in antigen-specific IgG1 Fc N-glycosylation upon influenza and tetanus vaccination. Mol Cell Proteomics. 2011; 11(4):M111.014563. PMC: 3322571. DOI: 10.1074/mcp.M111.014563. View

Tarhoni I, Fhied C, Pool M, Liptay M, Bonomi P, Seder C . Development of bead based multiplexed immunoassay for evaluation of midkine, syndecan-1, and ANGPTL4 in patient serum. J Immunoassay Immunochem. 2018; 39(1):84-98. PMC: 8328281. DOI: 10.1080/15321819.2017.1407338. View

Gunn B, Yu W, Karim M, Brannan J, Herbert A, Wec A . A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus. Cell Host Microbe. 2018; 24(2):221-233.e5. PMC: 6298217. DOI: 10.1016/j.chom.2018.07.009. View

10.

Menni C, Valdes A, Freidin M, Sudre C, Nguyen L, Drew D . Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med. 2020; 26(7):1037-1040. PMC: 7751267. DOI: 10.1038/s41591-020-0916-2. View

11.

Farlow E, Patel K, Basu S, Lee B, Kim A, Coon J . Development of a multiplexed tumor-associated autoantibody-based blood test for the detection of non-small cell lung cancer. Clin Cancer Res. 2010; 16(13):3452-62. DOI: 10.1158/1078-0432.CCR-09-3192. View

12.

Chakraborty S, Gonzalez J, Edwards K, Mallajosyula V, Buzzanco A, Sherwood R . Proinflammatory IgG Fc structures in patients with severe COVID-19. Nat Immunol. 2020; 22(1):67-73. PMC: 8130642. DOI: 10.1038/s41590-020-00828-7. View

13.

Irvine E, Alter G . Understanding the role of antibody glycosylation through the lens of severe viral and bacterial diseases. Glycobiology. 2020; 30(4):241-253. PMC: 7109349. DOI: 10.1093/glycob/cwaa018. View

14.

Hou H, Yang H, Liu P, Huang C, Wang M, Li Y . Profile of Immunoglobulin G -Glycome in COVID-19 Patients: A Case-Control Study. Front Immunol. 2021; 12:748566. PMC: 8495247. DOI: 10.3389/fimmu.2021.748566. View

15.

Van Coillie J, Pongracz T, Rahmoller J, Chen H, Geyer C, van Vught L . The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees. EBioMedicine. 2022; 87:104408. PMC: 9756879. DOI: 10.1016/j.ebiom.2022.104408. View

16.

Lofano G, Gorman M, Yousif A, Yu W, Fox J, Dugast A . Antigen-specific antibody Fc glycosylation enhances humoral immunity via the recruitment of complement. Sci Immunol. 2018; 3(26). PMC: 6298214. DOI: 10.1126/sciimmunol.aat7796. View

17.

Chen X, Rostad C, Anderson L, Sun H, Lapp S, Stephens K . The development and kinetics of functional antibody-dependent cell-mediated cytotoxicity (ADCC) to SARS-CoV-2 spike protein. Virology. 2021; 559:1-9. PMC: 7975276. DOI: 10.1016/j.virol.2021.03.009. View

18.

Pongracz T, Nouta J, Wang W, van Meijgaarden K, Linty F, Vidarsson G . Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19. EBioMedicine. 2022; 78:103957. PMC: 8938159. DOI: 10.1016/j.ebiom.2022.103957. View

19.

Tso F, Lidenge S, Poppe L, Pena P, Privatt S, Bennett S . Presence of antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 in COVID-19 plasma. PLoS One. 2021; 16(3):e0247640. PMC: 7932539. DOI: 10.1371/journal.pone.0247640. View

20.

Mamede J, Sitbon M, Battini J, Courgnaud V . Heterogeneous susceptibility of circulating SIV isolate capsids to HIV-interacting factors. Retrovirology. 2013; 10:77. PMC: 3751554. DOI: 10.1186/1742-4690-10-77. View