Cross-clade protective immune responses of NS1-truncated live attenuated H5N1 avian influenza vaccines |
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| Affiliation: | 1. College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, PR China;2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, PR China;3. Jiangsu Research Center of Engineering and Technology for the Prevention and Control of Poultry Disease, Yangzhou, Jiangsu, PR China;4. Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, PR China;1. Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA;2. Juvaris BioTherapeutics, Pleasanton, CA 94566, USA;3. Department of Pediatrics, Interdepartmental Program in Immunology, and Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA;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. College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China;2. Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou 510642, China;3. National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China;1. OIE/FAO and National Reference Laboratory for Newcastle Disease and Avian Influenza, OIE Collaborating Centre for Infectious Diseases at the Human-Animal Interface, Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), Viale dell’Università 10, 35020 Legnaro (PD), Italy;2. Research and Development Department, Boehringer Ingelheim Vetmedica, Mexico;3. Public Health and Risk Analysis Department, Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), Viale dell’Università 10, 35020 Legnaro (PD), Italy;1. Animal Health Biotechnology, Temasek Life Sciences Laboratory, Singapore, Singapore;2. Department of Microbiology Faculty of Medicine, National University of Singapore, Singapore, Singapore |
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| Abstract: | BackgroundH5N1 highly pathogenic avian influenza (HPAI) has raised global concern for causing huge economic losses in poultry industry, and an effective vaccine against HPAI is highly desirable. Live attenuated influenza vaccine with trunctated NS1 protein as a potential strategy will be extremely useful for improving immune efficacy.MethodsA series of H5N1 avian influenza virus reassortants harboring amino-terminal 48, 70, 73, and 99 aa in NS1 proteins, along with a modified low pathogenic HA protein was generated, and named as S-HALo/NS48, S-HALo/NS70, S-HALo/NS73, and S-HALo/NS99, respectively. In addition, their biological and immunological characteristics were further analyzed.ResultsThe viruses S-HALo/NS70, S-HALo/NS73, and S-HALo/NS99, but not S-HALo/NS48, had a comparable growth property with the full-length NS1 virus, S-HALo/NSFu. Mice and chickens studies demonstrated that the viruses with truncated NS1 protein were further attenuated when compared to the virus S-HALo/NSFu. Vaccination with the virus S-HALo/NS73 in chickens induced significant cross-protection against homologous clade 2.3.4 H5 virus and heterologous clade 7.2, 2.3.2.1, and 2.3.4.4 H5 viruses.ConclusionA 70-aa amino-terminal fragment of NS1 protein may be long enough for viral replication. The recombinant virus S-HALo/NS73 is a broad-spectrum live attenuated H5N1 avian influenza vaccine candidate in chickens. |
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| Keywords: | H5N1 avian influenza Live attenuated vaccine NS1 Cross-protection |
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