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Vaccination with virus-like particles containing H5 antigens from three H5N1 clades protects chickens from H5N1 and H5N8 influenza viruses
Affiliation:1. USDA SEPRL, Athens, GA, USA;2. Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA, USA;3. Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD, USA;1. Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China;2. Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China;3. College of veterinary Medicine, Inner Mongolia Agricultural University, Inner Mongolia Autonomous Region, Huhhot, China;4. College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin Province, China;5. College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang Province, China;6. Changchun SR Biological Technology Co., Ltd, Changchun, Jilin Province, China;7. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, China;8. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China;1. Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China;2. Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, China;3. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China;1. Avian Disease Laboratory, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea;2. Molecular Vaccinology Laboratory, International Vaccine Institute, Seoul 151-919, Republic of Korea;1. Food and Agriculture Organization of the United Nations (FAO), Regional Office for Asia and the Pacific, Bangkok, Thailand;2. Food and Agriculture Organization of the United Nations (FAO), Viale delle Terme Di Caracalla, Rome 00153, Italy;3. Influenza Division, Centers for Disease Control and Prevention, USA
Abstract:Highly pathogenic avian influenza (HPAI) viruses, especially H5N1 strains, represent a public health threat and cause widespread morbidity and mortality in domestic poultry. Recombinant virus-like particles (VLPs) represent a promising novel vaccine approach to control avian influenza including HPAI strains. Influenza VLPs contain viral hemagglutinin (HA), which can be expressed in cell culture within highly immunogenic VLPs that morphologically and antigenically resemble influenza virions, except VLPs are non-infectious. Here we describe a recombinant VLP containing HA proteins derived from three distinct clades of H5N1 viruses as an experimental, broadly protective H5 avian influenza vaccine. A baculovirus vector was configured to co-express the H5 genes from recent H5N1 HPAI isolates A/chicken/Germany/2014 (clade 2.3.4.4), A/chicken/West Java/Subang/29/2007 (clade 2.1.3) and A/chicken/Egypt/121/2012 (clade 2.2.1). Co-expression of these genes in Sf9 cells along with influenza neuraminidase (NA) and retrovirus gag genes resulted in production of triple-clade H555 VLPs that exhibited hemagglutination activity and morphologically resembled influenza virions. Vaccination of chickens with these VLPs resulted in induction of serum antibody responses and efficient protection against experimental challenges with three different viruses including the recent U.S. H5N8 HPAI isolate. We conclude that these novel triple-clade VLPs represent a feasible strategy for simultaneously evoking protective antibodies against multiple variants of H5 influenza virus.
Keywords:Avian influenza  Virus-like particle  VLP vaccine  Trivalent
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