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A vaccine candidate of attenuated genotype VII Newcastle disease virus generated by reverse genetics

机译:反向遗传学产生的减毒VII型新城疫病毒的候选疫苗

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Genotype VII Newcastle disease virus (NDV) has been documented as the predominant epidemic genotype in China and some other Asian countries since 1990s. Recent work has demonstrated that NDV vaccines phylogenetically closer to epidemic viruses provide better protection than conventional vaccines in terms of reducing virus shedding and transmission. Since there is currently no available vaccine which possesses a close antigenic relationship to the prevalent virulent NDV, a new vaccine to protect against the infection of this genotype NDV is in urgent need. Here, we describe the generation of a pathogenicity-attenuated genotype VII NDV (NDV/ZJ1HN) from a velogenic NDV by mutating the velogenic amino acid motif at the F protein cleavage site using reverse genetics techniques. The attenuated-pathogenicity of NDV/ZJ1HN was confirmed by examination of mean death time (MDT) in embryonated eggs and intracerebral pathogenicity index (ICPI) in day-old chickens. Subsequently, 2 weeks old birds were immunized with live and inactivated NDV/ZJ1HN-based vaccines and challenged 3 or 4 weeks post-immunization with a lethal dose of a virulent genotype VII NDV strain. Results showed that NDV/ZJ1HN effectively protected the vaccinated birds from morbidity and mortality against genotype VII virus challenge and significantly reduced virus shedding from the vaccinated birds when compared with La Sota vaccinated animals, suggesting that NDV/ZJ1HN is a promising vaccine candidate for the control of current ND epidemicin China.
机译:自从1990年代以来,基因型VII新城疫病毒(NDV)被证明是中国和其他一些亚洲国家的主要流行基因型。最近的工作表明,从病毒学角度看,NDV疫苗在系统发育上更接近流行病毒,在减少病毒散发和传播方面提供了比常规疫苗更好的保护。由于目前没有可用的疫苗与流行的强毒NDV具有密切的抗原关系,因此迫切需要一种新的疫苗来防止这种基因型NDV的感染。在这里,我们描述了通过使用反向遗传学技术通过突变F蛋白切割位点的velogenic氨基酸基序,从velogenic NDV产生致病性减弱的基因型VII NDV(NDV / ZJ1HN)。 NDV / ZJ1HN的致病性减弱是通过检查雏鸡的平均卵死亡时间(MDT)和脑内致病性指数(ICPI)来证实的。随后,用活的和灭活的基于NDV / ZJ1HN的疫苗对2周龄的禽类进行免疫,并在免疫后3或4周用致死剂量的有毒力的VII型NDV基因毒株进行攻击。结果表明,与La Sota疫苗接种的动物相比,NDV / ZJ1HN有效地保护了疫苗接种的禽鸟免受VII型基因病毒攻击的发病率和死亡率,并显着降低了从疫苗接种的禽鸟身上排出的病毒,这表明NDV / ZJ1HN是有望用于控制该疫苗的候选疫苗目前的ND流行病中国

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