• Jincun Zhao, Jingxian Zhao, Ashutosh K Mangalam, Rudragouda Channappanavar, Craig Fett, David K Meyerholz, Sudhakar Agnihothram, Ralph S Baric, Chella S David, and Stanley Perlman.
• 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.
• Immunity. 2016 Jun 21; 44 (6): 1379-91.

AbstractTwo 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.Copyright © 2016 Elsevier Inc. All rights reserved.

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