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

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  • Zhao, Jincun
    • Other Affiliation: Department of Microbiology; University of Iowa
  • Zhao, Jingxian
    • Other Affiliation: Department of Microbiology; University of Iowa
  • Mangalam, Ashutosh K.
    • Other Affiliation: Department of Pathology; University of Iowa
  • Channappanavar, Rudragouda
    • Other Affiliation: Department of Microbiology; University of Iowa
  • Fett, Craig
    • Other Affiliation: Department of Microbiology; University of Iowa
  • Meyerholz, David K.
    • Other Affiliation: Department of Pathology; University of Iowa
  • Agnihothram, Sudhakar
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
    • Other Affiliation: National Center for Toxicological Research; Food and Drug Administration
  • Baric, Ralph S.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • David, Chella S.
    • Other Affiliation: Department of Immunology; Mayo Clinic
  • Perlman, Stanley
    • Other Affiliation: Department of Microbiology; University of Iowa
Abstract
  • Two zoonotic coronaviruses (CoV), 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 interferon-γ-dependent 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 may have broad applicability in the context of new CoV and other respiratory virus outbreaks.
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  • Article
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  • In Copyright
Journal title
  • Immunity
Journal volume
  • 44
Journal issue
  • 6
Language
  • English
ISSN
  • 1097-4180
  • 1074-7613

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