Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses.
Identifieur interne : 001087 ( PubMed/Corpus ); précédent : 001086; suivant : 001088Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses.
Auteurs : Jincun Zhao ; Jingxian Zhao ; Ashutosh K. Mangalam ; Rudragouda Channappanavar ; Craig Fett ; David K. Meyerholz ; Sudhakar Agnihothram ; Ralph S. Baric ; Chella S. David ; Stanley PerlmanSource :
- Immunity [ 1097-4180 ] ; 2016.
English descriptors
- KwdEn :
- 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).
- MESH :
- chemical , immunology : Antigens, Viral, Epitopes, T-Lymphocyte, Viral Vaccines.
- immunology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Coronavirus Infections, Respiratory System, SARS Virus, Severe Acute Respiratory Syndrome, Virion.
- chemical , metabolism : Interferon-gamma.
- virology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes.
- Animals, Cells, Cultured, Cross Reactions, Humans, Immunity, Immunologic Memory, Mice, Mice, Inbred Strains, Vaccination.
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.
DOI: 10.1016/j.immuni.2016.05.006
PubMed: 27287409
Links to Exploration step
pubmed:27287409Le document en format XML
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<front><div type="abstract" xml:lang="en">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.</div>
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