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

Immunity. 2016 Jun 21;44(6):1379-91. doi: 10.1016/j.immuni.2016.05.006. Epub 2016 Jun 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Coronavirus Infections / immunology*
  • Cross Reactions
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Immunity
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred Strains
  • Respiratory System / immunology*
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / immunology*
  • Vaccination
  • Viral Vaccines / immunology*
  • Virion / immunology

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Viral Vaccines
  • Interferon-gamma