A novel genotype VII Newcastle disease virus vaccine candidate generated by mutation in the L and F genes confers improved protection in chickens

Authors: JI, YANHONG - Lanzhou Institute Of Veterinary Research; LIU, TAO - Anhui Agricultural University; DU, YINGYING - Lanzhou Institute Of Veterinary Research; CUI, XIAOLE - Lanzhou Institute Of Veterinary Research; Yu, Qingzhong; WANG, ZHENGXIANG - Lanzhou Institute Of Veterinary Research; ZHANG, JINJIN - Lanzhou Institute Of Veterinary Research; LI, YU - Lanzhou Institute Of Veterinary Research; ZHU, QIYUN - Lanzhou Institute Of Veterinary Research

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/30/2018
Publication Date: 3/1/2018
Citation: Ji, Y., Liu, T., Du, Y., Cui, X., Yu, Q., Wang, Z., Li, Y., Zhu, Q. 2018. A novel genotype VII Newcastle disease virus vaccine candidate generated by mutation in the L and F genes confers improved protection in chickens. Veterinary Microbiology. 216:99-106. https://doi.org/10.1016/j.vetmic.2018.01.021.
DOI: https://doi.org/10.1016/j.vetmic.2018.01.021

Interpretive Summary: Newcastle disease (ND), caused by infection of virulent Newcastle disease virus (NDV), is one of the most economically important infectious diseases of poultry. Administration of vaccines combined with the good management and strict biosecurity is an effective way for control of this disease. However, vaccine failure is continuously reported in some countries mainly because new NDV strains have emerged that are antigenically different from commonly used vaccine strains. In this study, we aimed to develop an antigen-matched ND vaccine using reverse genetics technology to improve vaccine efficacy in birds. A virulent genotype VII NDV G7 strain commonly circulated in some Asian countries was modified by introducing mutations in the F and L genes of the virus, resulting in a new mutant, G7M. Biological characterization showed that G7M was safe and genetically stable after serial passages in embryos and chickens. Vaccination of chickens with G7M conferred full protection against genotype VII NDV challenge, and more importantly, it effectively reduced the challenge virus shedding in chickens. Together, our data suggest that G7M is a promising genotype VII vaccine candidate, and the novel attenuation approach designed in this study could be used to develop new antigen-matched NDV vaccines.

Technical Abstract: Administration of vaccines combined with the good management and strict biosecurity is an e'ective way for Newcastle disease (ND) control. However, vaccine failure is continuously reported in some countries mainly because the antigenic di'erence between the used vaccine and 'eld strains even they are of one serotype. Therefore, development of antigen-matched ND vaccines is needed to improve the vaccine e'cacy in birds. In this study, we introduced four site mutations, K1756A, D1881A, K1917A and E1954Q, respectively, into the large protein gene of the virulent genotype VII Newcastle disease virus (NDV) G7 strain using reverse genetics technology. Four rescued NDVs were sharply attenuated for the pathogenicity in chickens. One of these mutants, E1954Q, was further manipulated by replacing the F cleavage site sequence of typical velogenic strains with that of the LaSota vaccine, resulting in a new mutant, G7M. Biological characterization showed that G7M was safe and genetically stable after serial passages in embryos and chickens. Vaccination of chickens with G7M induced a progressive elevation of the homologous antibodies and markedly higher CD8 + T cell percentage, T cell proliferation and IFN-' than LaSota. G7M conferred full protection against genotype VII NDV challenge, and more importantly, it e'ectively reduced the challenge virus replication and shedding in chickens. Together, our data suggest that G7M is a promising genotype VII vaccine candidate, and the novel attenuation approach designed in this study could be used to develop new antigen-matched NDV vaccines