Chimpanzee adenovirus vector-based avian influenza vaccine completely protects mice against lethal challenge of H5N1 |
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Affiliation: | 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, China;2. National Institutes for Food and Drug Control, Beijing, China;3. Beijing Wantai Biological Pharmacy Enterprise, Beijing, China;1. The Research Institute for Biological Safety Problems, Zhambulskaya oblast, Kordaiskiy rayon, 080409, Gvardeiskiy, Kazakhstan;2. Faculty of Veterinary Science, Kazakh National Agrarian University (KazNAU), Almaty 050010, Kazakhstan;3. Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University (OSU), Wooster, OH 44691, USA |
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Abstract: | Highly pathogenic avian H5N1 viruses may give rise to the next influenza pandemic due to their reassortment and mutation of the genome. Vaccine against this virus is important for coping with its potential threat. Chimpanzee adenovirus (Ad) vectors are a novel type of vaccine vectors that share the advantages of human serotype Ad vectors but without being affected by pre-existing human neutralizing antibody to the vaccine vector. Based on a replication-deficient chimpanzee Ad vector, AdC7, we generated a novel H5N1 vaccine candidate AdC7-H5HA that expresses H5N1 Hemagglutinin (HA). When tested in mice, the vaccine significantly reduced the virus load and pathological lesions in the lung tissues, and conferred complete protection against lethal challenge by a homologous virus. Mechanistically, the AdC7-H5HA vaccine can induce both HA-specific humoral and cell-mediated immune responses in mice. Also, sera transfer experiments demonstrated that neutralizing antibodies alone could provide protection. In conclusion, our results show that chimpanzee Ad vector expressing influenza virus HA may represent a promising vaccine candidate for H5N1 viruses and other influenza virus subtypes. |
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Keywords: | Influenza H5N1 AdC7 Vaccine Immune responses |
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