Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses

Jincun Zhao; Jingxian Zhao; Ashutosh K Mangalam; Rudragouda Channappanavar; Craig Fett; David K Meyerholz; Sudhakar Agnihothram; Ralph S Baric; Chella S David; Stanley Perlman

doi:10.1016/j.immuni.2016.05.006

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Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses

Journal article

Open access

Peer reviewed

Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses

Jincun Zhao, Jingxian Zhao, Ashutosh K Mangalam, Rudragouda Channappanavar, Craig Fett, David K Meyerholz, Sudhakar Agnihothram, Ralph S Baric, Chella S David and Stanley Perlman

Immunity, Vol.44(6), pp.1379-1391

06/21/2016

DOI: 10.1016/j.immuni.2016.05.006

PMCID: PMC4917442

PMID: 27287409

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Abstract

Two zoonotic coronaviruses (CoVs)-SARS-CoV and MERS-CoV-have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4(+) T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4(+) T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was dependent on interferon-γ and required early induction of robust innate and virus-specific CD8(+) T cell responses. The conserved epitope was also recognized in SARS-CoV- and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4(+) T cells targeting conserved epitopes might have broad applicability in the context of new CoVs and other respiratory virus outbreaks.

SARS Virus - immunology

Virion - immunology

Humans

Vaccination

Cells, Cultured

Severe Acute Respiratory Syndrome - immunology

Interferon-gamma - metabolism

Mice, Inbred Strains

Coronavirus Infections - immunology

Immunity

CD4-Positive T-Lymphocytes - immunology

Cross Reactions

Antigens, Viral - immunology

Animals

CD8-Positive T-Lymphocytes - virology

Immunologic Memory

Mice

Epitopes, T-Lymphocyte - immunology

CD4-Positive T-Lymphocytes - virology

CD8-Positive T-Lymphocytes - immunology

Viral Vaccines - immunology

Respiratory System - immunology

Details

Title: Subtitle: Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses
Creators: Jincun Zhao - University of Iowa
Jingxian Zhao - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Ashutosh K Mangalam - Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Rudragouda Channappanavar - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Craig Fett - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
David K Meyerholz - Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Sudhakar Agnihothram - Department of Microbiology and Immunology and Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA
Ralph S Baric - Department of Microbiology and Immunology and Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA
Chella S David - Department of Immunology, Mayo Clinic, Rochester, MI 55905, USA
Stanley Perlman - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. Electronic address: stanley-perlman@uiowa.edu
Resource Type: Journal article
Publication Details: Immunity, Vol.44(6), pp.1379-1391
DOI: 10.1016/j.immuni.2016.05.006
PMID: 27287409
PMCID: PMC4917442
NLM abbreviation: Immunity
ISSN: 1097-4180
eISSN: 1097-4180
Publisher: United States
Grant note: P01 AI060699 / NIAID NIH HHS R01 AI091322 / NIAID NIH HHS U19 AI100625 / NIAID NIH HHS
Language: English
Date published: 06/21/2016
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777471602771

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