Journal article
Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection
Emerging Microbes & Infections, Vol.8(1), pp.760-772
01/01/2019
DOI: 10.1080/22221751.2019.1620083
PMCID: PMC6542157
PMID: 31130102
Abstract
The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.
Details
- Title: Subtitle
- Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection
- Creators
- Wenxu Jia - Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityRudragouda Channappanavar - Department of Acute and Tertiary Care, and the Institute for the Study of Host-Pathogen Systems, University of Tennessee Health Science CenterChao Zhang - Key Laboratory of Molecular Virology & Immunology, Vaccine Research Center, Institut Pasteur of Shanghai, Chinese Academy of SciencesMingxi Li - Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityHaixia Zhou - The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua UniversityShuyuan Zhang - The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua UniversityPanpan Zhou - Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityJiuyang Xu - Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversitySisi Shan - Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityXuanling Shi - Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityXinquan WangJincun Zhao - State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityDongming Zhou - Key Laboratory of Molecular Virology & Immunology, Vaccine Research Center, Institut Pasteur of Shanghai, Chinese Academy of SciencesStanley Perlman - University of Iowa, Stead Family Department of PediatricsLinqi Zhang - Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University
- Resource Type
- Journal article
- Publication Details
- Emerging Microbes & Infections, Vol.8(1), pp.760-772
- DOI
- 10.1080/22221751.2019.1620083
- PMID
- 31130102
- PMCID
- PMC6542157
- NLM abbreviation
- Emerg Microbes Infect
- ISSN
- 2222-1751
- eISSN
- 2222-1751
- Publisher
- Taylor & Francis; Abington
- Grant note
- XBD29040000 / Chinese Academy of Science (10.13039/501100002367) 2018ZX10101004; 2016YFC1201000; 2017ZX10201101; 2018ZX10731101 / National Science and Technology Development Agency (10.13039/501100004192) 81530065; 81471929 / National Natural Science Foundation of China (10.13039/501100001809) N.I.H (10.13039/100000098) 81661128042 / Grand Challenges China 2016YFC1200902 / National Plan on Key Basic Research and Development
- Language
- English
- Date published
- 01/01/2019
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983782098702771
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