Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.
Jiangsu Co-Innovation Center for the Prevention and Control of Animal Infectious Disease and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Viruses. 2022 Dec 28;15(1):82. doi: 10.3390/v15010082.
Genotype VII Newcastle Disease Virus (NDV) has caused a pandemic in many countries and usually causes fatal consequences in infected chickens. Although current commercial attenuated NDV vaccines can provide an ideal protection against genotype VII NDV, they cannot completely prevent the infection and viral shedding, and the genotype of some vaccine strains cannot match with the prevalent strain. In this study, in order to construct a thermostable and genotype VII-matched live attenuated vaccine, we used a thermostable genotype VIII virulent HR09 strain as the backbone and replaced its F gene with that of the genotype VII DT-2014 strain. Meanwhile, the cleavage site of F gene of DT-2014 was mutated to that of class I F protein and avirulent class II F protein, respectively. The results showed that the two chimeric viruses, designated rcHR09-CI and rcHR09-CII, shared a similar growth kinetics and thermostability with their parental HR09 strain. Mean death time (MDT) and intracerebral pathogenicity index (ICPI) tests showed that the two chimeric viruses were highly attenuated. Though both chimeric NDVs and La Sota vaccine strain could provide complete protection to immunized chickens against the challenge of virulent genotype VII ZJ1 strain, the two chimeric NDVs could induce a higher level of antibody response against ZJ1 strain and could significantly reduce the viral shedding compared with La Sota vaccine strain. In conclusion, our study constructed two chimeric thermostable genotype VII-matched NDV vaccine candidates, which provided complete protection against the challenge of virulent genotype VII NDV.
基因 VII 型新城疫病毒(NDV)已在许多国家引发大流行,通常会导致感染鸡致命后果。尽管目前的商业减毒 NDV 疫苗可以为基因 VII 型 NDV 提供理想的保护,但它们不能完全阻止感染和病毒脱落,而且一些疫苗株的基因型与流行株不匹配。在这项研究中,为了构建一种耐热且与基因 VII 型匹配的活减毒疫苗,我们使用耐热的基因 VIII 毒力 HR09 株作为骨架,并用基因 VII 型 DT-2014 株替换其 F 基因。同时,将 DT-2014 株 F 基因的裂解位点分别突变为 I 类 F 蛋白和无毒性的 II 类 F 蛋白。结果表明,两种嵌合病毒,分别命名为 rcHR09-CI 和 rcHR09-CII,与亲本 HR09 株具有相似的生长动力学和耐热性。平均死亡时间(MDT)和脑内致病指数(ICPI)试验表明,两种嵌合病毒高度减毒。虽然两种嵌合 NDV 与 La Sota 疫苗株均可对免疫鸡提供完全保护,免受强毒基因 VII 型 ZJ1 株的攻击,但两种嵌合 NDV 可诱导针对 ZJ1 株更高水平的抗体反应,并可显著降低与 La Sota 疫苗株相比的病毒脱落。总之,我们的研究构建了两种耐热且与基因 VII 型匹配的嵌合 NDV 疫苗候选株,可完全抵抗强毒基因 VII 型 NDV 的攻击。