Evaluation of adenovirus 19a as a novel vector for mucosal vaccination against influenza A viruses |
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| Institution: | 1. Department of Molecular and Medical Virology, Ruhr-University Bochum, Universitätsstraße 150, 44790 Bochum, Germany;2. Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Schloßgarten 4, 91054 Erlangen, Germany;3. Institute for Virology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany;4. Sirion Biotech, Am Klopferspitz 19, 82152 Martinsried, Germany;1. Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Denmark;2. Department of Mathematical Sciences, University of Copenhagen, Denmark;3. Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark;4. NIA, NIH, Baltimore MD, USA;5. InProTher ApS, DK2200 Copenhagen, Denmark;1. Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore;2. Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore;3. Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China;1. Joint National Laboratory for Antibody Drug Engineering, Henan University, School of Basic Medical Sciences, Kaifeng, Henan Province, China;2. Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China;3. Key Lab of Cellular and Molecular Immunology, Henan University, School of Basic Medical Sciences, Kaifeng, Henan Province, China;4. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, China;5. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China;6. Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China;1. Institute of Clinical and Molecular Virology, University Hospital Erlangen, Universitätsklinikum Erlangen Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany;2. Mikrobiologisches Institut—Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany;3. University Hospital of Cologne, Faculty of Medicine, Department I of Internal Medicine, Cologne, Germany;4. University of Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Cologne, Germany;5. Institute of Virology, School of Medicine, Technical University of Munich/Helmholtz Zentrum München, 81675 Munich, Germany;6. Institute of Molecular Immunology and Experimental Oncology, School of Medicine, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany;7. DZIF, partner sites Munich and Cologne/Bonn, Germany |
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| Abstract: | Since preexisting immunity and enhanced infection rates in a clinical trial of an HIV vaccine have raised some concerns on adenovirus (Ad) serotype 5-based vaccines, we evaluated the subgroup D adenovirus serotype Ad19a for its suitability as novel viral vector vaccine against mucosal infections. In BALB/c mice, we compared the immunogenicity and efficacy of E1/E3-deleted Ad19a vectors encoding the influenza A virus (IAV)-derived antigens hemagglutinin (HA) and nucleoprotein (NP) to the most commonly used Ad5 vectors. The adenoviral vectors were applied intranasally and induced detectable antigen-specific T cell responses in the lung and in the spleen as well as robust antibody responses. A prior DNA immunization significantly improved the immunogenicity of both vectors and resulted in full protection against a lethal infection with a heterologous H3N2 virus. Nevertheless, the Ad5-based vectors were slightly superior in reducing viral replication in the lung which corresponded to higher NP-specific T cell responses measured in the lungs. |
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| Keywords: | Adenoviral vectors Ad19a Ad5 Influenza A virus Mucosal vaccines |
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