Antibodies Targeting Conserved Non-canonical Antigens and Endemic Coronaviruses Associate with Favorable Outcomes in Severe COVID-19

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 Jun 23

PMID 35738278

Authors

Sai Preetham Peddireddy

Syed A Rahman

Anthony R Cillo

Godhev Manakkat Vijay

Ashwin Somasundaram

Creg J Workman

William Bain

Bryan J McVerry

Barbara Methe

Janet S Lee

Prabir Ray

Anuradha Ray

Tullia C Bruno

Dario A A Vignali

Georgios D Kitsios

Alison Morris

Harinder Singh

Aniruddh Sarkar

Jishnu Das

Affiliations

Soon will be listed here.

Abstract

While there have been extensive analyses characterizing cellular and humoral responses across the severity spectrum in COVID-19, outcome predictors within severe COVID-19 remain less comprehensively elucidated. Furthermore, properties of antibodies (Abs) directed against viral antigens beyond spike and their associations with disease outcomes remain poorly defined. We perform deep molecular profiling of Abs directed against a wide range of antigenic specificities in severe COVID-19 patients. The profiles included canonical (spike [S], receptor-binding domain [RBD], and nucleocapsid [N]) and non-canonical (orf3a, orf8, nsp3, nsp13, and membrane [M]) antigenic specificities. Notably, multivariate Ab profiles directed against canonical or non-canonical antigens are equally discriminative of survival in severe COVID-19. Intriguingly, pre-pandemic healthy controls have cross-reactive Abs directed against nsp13, a protein conserved across coronaviruses. Consistent with these findings, a model built on Ab profiles for endemic coronavirus antigens also predicts COVID-19 outcome. Our results suggest the importance of studying Abs targeting non-canonical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and endemic coronavirus antigens in COVID-19.

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References

Loyal L, Braun J, Henze L, Kruse B, Dingeldey M, Reimer U . Cross-reactive CD4 T cells enhance SARS-CoV-2 immune responses upon infection and vaccination. Science. 2021; 374(6564):eabh1823. PMC: 10026850. DOI: 10.1126/science.abh1823. View

Ackerman M, Das J, Pittala S, Broge T, Linde C, Suscovich T . Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV. Nat Med. 2018; 24(10):1590-1598. PMC: 6482471. DOI: 10.1038/s41591-018-0161-0. View

To K, Zhang A, Hung I, Xu T, Ip W, Wong R . High titer and avidity of nonneutralizing antibodies against influenza vaccine antigen are associated with severe influenza. Clin Vaccine Immunol. 2012; 19(7):1012-8. PMC: 3393364. DOI: 10.1128/CVI.00081-12. View

Aydillo T, Rombauts A, Stadlbauer D, Aslam S, Abelenda-Alonso G, Escalera A . Immunological imprinting of the antibody response in COVID-19 patients. Nat Commun. 2021; 12(1):3781. PMC: 8213790. DOI: 10.1038/s41467-021-23977-1. View

LaMere M, Moquin A, Lee F, Misra R, Blair P, Haynes L . Regulation of antinucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance. J Virol. 2011; 85(10):5027-35. PMC: 3126167. DOI: 10.1128/JVI.00150-11. View

Sadarangani M, Marchant A, Kollmann T . Immunological mechanisms of vaccine-induced protection against COVID-19 in humans. Nat Rev Immunol. 2021; 21(8):475-484. PMC: 8246128. DOI: 10.1038/s41577-021-00578-z. View

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

Gordon D, Jang G, Bouhaddou M, Xu J, Obernier K, White K . A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020; 583(7816):459-468. PMC: 7431030. DOI: 10.1038/s41586-020-2286-9. View

Lu L, Das J, Grace P, Fortune S, Restrepo B, Alter G . Antibody Fc Glycosylation Discriminates Between Latent and Active Tuberculosis. J Infect Dis. 2020; 222(12):2093-2102. PMC: 7661770. DOI: 10.1093/infdis/jiz643. View

10.

Swadling L, Diniz M, Schmidt N, Amin O, Chandran A, Shaw E . Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature. 2021; 601(7891):110-117. PMC: 8732273. DOI: 10.1038/s41586-021-04186-8. View

11.

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

12.

Hoepel W, Chen H, Geyer C, Allahverdiyeva S, Manz X, de Taeye S . High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages. Sci Transl Med. 2021; 13(596). PMC: 8158960. DOI: 10.1126/scitranslmed.abf8654. View

13.

Lee W, Wheatley A, Kent S, DeKosky B . Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol. 2020; 5(10):1185-1191. DOI: 10.1038/s41564-020-00789-5. View

14.

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

15.

Hachim A, Kavian N, Cohen C, Chin A, Chu D, Mok C . ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection. Nat Immunol. 2020; 21(10):1293-1301. DOI: 10.1038/s41590-020-0773-7. View

16.

Guo L, Wang Y, Kang L, Hu Y, Wang L, Zhong J . Cross-reactive antibody against human coronavirus OC43 spike protein correlates with disease severity in COVID-19 patients: a retrospective study. Emerg Microbes Infect. 2021; 10(1):664-676. PMC: 8023607. DOI: 10.1080/22221751.2021.1905488. View

17.

Zohar T, Loos C, Fischinger S, Atyeo C, Wang C, Slein M . Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality. Cell. 2020; 183(6):1508-1519.e12. PMC: 7608014. DOI: 10.1016/j.cell.2020.10.052. View

18.

Atyeo C, Fischinger S, Zohar T, Slein M, Burke J, Loos C . Distinct Early Serological Signatures Track with SARS-CoV-2 Survival. Immunity. 2020; 53(3):524-532.e4. PMC: 7392190. DOI: 10.1016/j.immuni.2020.07.020. View

19.

Sadanand S, Das J, Chung A, Schoen M, Lane S, Suscovich T . Temporal variation in HIV-specific IgG subclass antibodies during acute infection differentiates spontaneous controllers from chronic progressors. AIDS. 2017; 32(4):443-450. PMC: 5983383. DOI: 10.1097/QAD.0000000000001716. View

20.

Shrock E, Fujimura E, Kula T, Timms R, Lee I, Leng Y . Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity. Science. 2020; 370(6520). PMC: 7857405. DOI: 10.1126/science.abd4250. View