Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses.
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.
State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China; Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. Electronic address: zhaojincun@gird.cn.
Jincun
J
Zhao
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Jingxian
J
Zhao
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
Ashutosh K
AK
Mangalam
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Rudragouda
R
Channappanavar
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Craig
C
Fett
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
David K
DK
Meyerholz
Department of Microbiology and Immunology and Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
Sudhakar
S
Agnihothram
Department of Microbiology and Immunology and Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
Ralph S
RS
Baric
Department of Immunology, Mayo Clinic, Rochester, MI 55905, USA.
Chella S
CS
David
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. Electronic address: stanley-perlman@uiowa.edu.
Stanley
S
Perlman
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D018352:Coronavirus Infections / Q000276:immunology*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007109:Immunity; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D012137:Respiratory System / Q000276:immunology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology*; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D014765:Viral Vaccines; D007371:Interferon-gamma