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Vaccine. 2020 Jan 11. pii: S0264-410X(19)31718-9. doi: 10.1016/j.vaccine.2019.12.054. [Epub ahead of print] Characterization of thermostable Newcastle disease virus recombinants expressing the hemagglutinin of H5N1 avian influenza virus as bivalent vaccine candidates.
Xu L1, Qin Z1, Qiao L1, Wen J1, Shao H2, Wen G3, Pan Z4.
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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.
Copyright ? 2019 Elsevier Ltd. All rights reserved.
KEYWORDS:
Hemagglutinin; Highly pathogenic avian influenza H5N1 virus; Newcastle disease virus; Thermostability; Vector vaccine
PMID: 31937412 DOI: 10.1016/j.vaccine.2019.12.054