Pre-existing Humoral Immunity to Human Common Cold Coronaviruses Negatively Impacts the Protective SARS-CoV-2 Antibody Response

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2021 Dec 29

PMID 34965382

Citations 57

Authors

Chun-Yang Lin

Joshua Wolf

David C Brice

Yilun Sun

Macauley Locke

Sean Cherry

Ashley H Castellaw

Marie Wehenkel

Jeremy Chase Crawford

Veronika I Zarnitsyna

Daniel Duque

Kim J Allison

E Kaitlynn Allen

Scott A Brown

Alexandra H Mandarano

Jeremie H Estepp

Charles Taylor

Carmen Molina-Paris

Stacey Schultz-Cherry

Li Tang

Paul G Thomas

Maureen A McGargill

Affiliations

Soon will be listed here.

Abstract

SARS-CoV-2 infection causes diverse outcomes ranging from asymptomatic infection to respiratory distress and death. A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoVs) impacts susceptibility to SARS-CoV-2 infection or immunity following infection and vaccination. Therefore, we analyzed samples from the same individuals before and after SARS-CoV-2 infection or vaccination. We found hCCCoV antibody levels increase after SARS-CoV-2 exposure, demonstrating cross-reactivity. However, a case-control study indicates that baseline hCCCoV antibody levels are not associated with protection against SARS-CoV-2 infection. Rather, higher magnitudes of pre-existing betacoronavirus antibodies correlate with more SARS-CoV-2 antibodies following infection, an indicator of greater disease severity. Additionally, immunization with hCCCoV spike proteins before SARS-CoV-2 immunization impedes the generation of SARS-CoV-2-neutralizing antibodies in mice. Together, these data suggest that pre-existing hCCCoV antibodies hinder SARS-CoV-2 antibody-based immunity following infection and provide insight on how pre-existing coronavirus immunity impacts SARS-CoV-2 infection, which is critical considering emerging variants.

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References

Lapp S, Edara V, Lu A, Lai L, Hussaini L, Chahroudi A . Original antigenic sin responses to Betacoronavirus spike proteins are observed in a mouse model, but are not apparent in children following SARS-CoV-2 infection. PLoS One. 2021; 16(8):e0256482. PMC: 8396729. DOI: 10.1371/journal.pone.0256482. View

Amanat F, Stadlbauer D, Strohmeier S, Nguyen T, Chromikova V, McMahon M . A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med. 2020; 26(7):1033-1036. PMC: 8183627. DOI: 10.1038/s41591-020-0913-5. View

Cohen K, Linderman S, Moodie Z, Czartoski J, Lai L, Mantus G . Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells. Cell Rep Med. 2021; 2(7):100354. PMC: 8253687. DOI: 10.1016/j.xcrm.2021.100354. 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

Gu Z, Eils R, Schlesner M . Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics. 2016; 32(18):2847-9. DOI: 10.1093/bioinformatics/btw313. View

Li S, Rouphael N, Duraisingham S, Romero-Steiner S, Presnell S, Davis C . Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat Immunol. 2013; 15(2):195-204. PMC: 3946932. DOI: 10.1038/ni.2789. View

Henry C, Palm A, Krammer F, Wilson P . From Original Antigenic Sin to the Universal Influenza Virus Vaccine. Trends Immunol. 2017; 39(1):70-79. PMC: 5748348. DOI: 10.1016/j.it.2017.08.003. 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

Gouma S, Weirick M, Bolton M, Arevalo C, Goodwin E, Anderson E . Health care worker seromonitoring reveals complex relationships between common coronavirus antibodies and COVID-19 symptom duration. JCI Insight. 2021; 6(16). PMC: 8410018. DOI: 10.1172/jci.insight.150449. View

10.

Nguyen-Contant P, Embong A, Kanagaiah P, Chaves F, Yang H, Branche A . S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit. mBio. 2020; 11(5). PMC: 7520599. DOI: 10.1128/mBio.01991-20. View

11.

Ng K, Faulkner N, Cornish G, Rosa A, Harvey R, Hussain S . Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science. 2020; 370(6522):1339-1343. PMC: 7857411. DOI: 10.1126/science.abe1107. View

12.

Sagar M, Reifler K, Rossi M, Miller N, Sinha P, White L . Recent endemic coronavirus infection is associated with less-severe COVID-19. J Clin Invest. 2020; 131(1). PMC: 7773342. DOI: 10.1172/JCI143380. View

13.

Dugan H, Guthmiller J, Arevalo P, Huang M, Chen Y, Neu K . Preexisting immunity shapes distinct antibody landscapes after influenza virus infection and vaccination in humans. Sci Transl Med. 2020; 12(573). PMC: 8115023. DOI: 10.1126/scitranslmed.abd3601. View

14.

Dugas M, Grote-Westrick T, Merle U, Fontenay M, Kremer A, Hanses F . Lack of antibodies against seasonal coronavirus OC43 nucleocapsid protein identifies patients at risk of critical COVID-19. J Clin Virol. 2021; 139:104847. PMC: 8065244. DOI: 10.1016/j.jcv.2021.104847. View

15.

Oshansky C, Gartland A, Wong S, Jeevan T, Wang D, Roddam P . Mucosal immune responses predict clinical outcomes during influenza infection independently of age and viral load. Am J Respir Crit Care Med. 2013; 189(4):449-62. PMC: 3977720. DOI: 10.1164/rccm.201309-1616OC. View

16.

Dobano C, Santano R, Jimenez A, Vidal M, Chi J, Rodrigo Melero N . Immunogenicity and crossreactivity of antibodies to the nucleocapsid protein of SARS-CoV-2: utility and limitations in seroprevalence and immunity studies. Transl Res. 2021; 232:60-74. PMC: 7879156. DOI: 10.1016/j.trsl.2021.02.006. View

17.

Selva K, van de Sandt C, Lemke M, Lee C, Shoffner S, Chua B . Systems serology detects functionally distinct coronavirus antibody features in children and elderly. Nat Commun. 2021; 12(1):2037. PMC: 8016934. DOI: 10.1038/s41467-021-22236-7. View

18.

Monto A, Malosh R, Petrie J, Martin E . The Doctrine of Original Antigenic Sin: Separating Good From Evil. J Infect Dis. 2017; 215(12):1782-1788. PMC: 5853211. DOI: 10.1093/infdis/jix173. View

19.

Dugan H, Stamper C, Li L, Changrob S, Asby N, Halfmann P . Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets. Immunity. 2021; 54(6):1290-1303.e7. PMC: 8101792. DOI: 10.1016/j.immuni.2021.05.001. View

20.

Legros V, Denolly S, Vogrig M, Boson B, Siret E, Rigaill J . A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity. Cell Mol Immunol. 2021; 18(2):318-327. PMC: 7786875. DOI: 10.1038/s41423-020-00588-2. View