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

作者：Zhao, Jincun^*; Zhao, Jingxian; Mangalam, Ashutosh K.; Channappanavar, Rudragouda; Fett, Craig; Meyerholz, David K.; Agnihothram, Sudhakar; Baric, Ralph S.; David, Chella S.; Perlman, Stanley^*

来源：Immunity, 2016, 44(6): 1379-1391.

DOI：10.1016/j.immuni.2016.05.006

• VIRUS-INFECTION
• RECOVERED PATIENTS
• BALB/C MICE
• RESPONSES
• INFLUENZA
• RECEPTOR
• VACCINE
• PROTEIN
• GENERATION
• DISEASE

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-gamma 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.

• 单位
  1; 广州医学院