Characterization of thermostable Newcastle disease virus recombinants expressing the hemagglutinin of H5N1 avian influenza virus as bivalent vaccine candidates |
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| Affiliation: | 1. IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain;2. Alternative Gene Expression S.L. ALGENEX, Centro empresarial – Parque Científico y Tecnológico Universidad Politécnica de Madrid Campus de Montegancedo, 28223 Pozuelo de Alarcón, Spain;3. Biomed Protection, Galveston, 77550 TX, USA;1. US National Poultry Research Center, Southeast Poultry Research Laboratory, Agricultural Research Services, United States Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA;2. Poultry Diagnostic and Research Center, Department of Population Health, College of Veterinary Medicine, The University of Georgia, 953 College Station Road, Athens, GA 30602, USA;1. Recombinant DNA Lab, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, India;2. Institute of Marine & Environmental Technology, University of Maryland Baltimore County, Baltimore, USA |
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| Abstract: | Newcastle disease virus (NDV) has been used as a vector in the development of vaccines and gene delivery. In the present study, we generated the thermostable recombinant NDV (rNDV) expressing the different forms of hemagglutinin (HA) of highly pathogenic avian influenza virus (HPAIV) H5N1 based on the full-length cDNA clone of thermostable TS09-C strain. The recombinant thermostable Newcastle disease viruses, rTS-HA, rTS-HA1 and rTS-tPAs/HA1, expressed the HA, HA1 or modified HA1 protein with the tissue plasminogen activator signal sequence (tPAs), respectively. The rNDVs displayed similar thermostability, growth kinetics and pathogenicity compared with the parental TS09-C virus. The tPAs facilitated the expression and secretion of HA1 protein in cells infected with rNDV. Animal studies demonstrated that immunization with rNDVs elicited effective H5N1- and NDV-specific antibody responses and conferred immune protection against lethal H5N1 and NDV challenges in chickens and mice. Importantly, vaccination of rTS-tPAs/HA1 resulted in enhanced protective immunity in chickens and mice. Our study thus provides a novel thermostable NDV-vectored vaccine candidate expressing a soluble form of a heterologous viral protein, which will greatly aid the poultry industry in developing countries. |
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| Keywords: | Newcastle disease virus Hemagglutinin Highly pathogenic avian influenza H5N1 virus Vector vaccine Thermostability |
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