College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
College of Animal Husbandry and Veterinary Medicine, Southwest University for Nationalities, Chengdu 610041, China.
Vet Microbiol. 2023 Oct;285:109872. doi: 10.1016/j.vetmic.2023.109872. Epub 2023 Sep 8.
Vaccines are widely used to prevent Newcastle disease virus (NDV). Under the pressure of immunization, NDVs with mutations among epitopes of F and HN protein were isolated, which indicates that the efficiency of vaccine may decrease in terms of preventing emerged NDV. However, the lack of evidences to support whether these mutations contribute to antigenic mutation and immune escape in NDV leading to the controversy that the matched vaccine is more effective than the mismatched vaccine. In this study, a genotype VII velogenic NDV strain (C22) was isolated from a vaccinated farm in Tibet, China. We found that this strain was close to NDV from east China, but it had a specific mutation (K138R) in one epitope (DYIGGIGKE) of HN protein. This mutation might change the interaction between amino acids in stalk-head link region of HN protein and then induce the specific antibody to worse recognize the C22 strain, but it did not alter viral virulence and growth ability. Then, the C22 strain was attenuated via modification of the F protein cleavage site to generate a matched vaccine. Comparing to a mismatched vaccine (LaSota), this matched vaccine showed advantages in inhibiting viral shedding and tissue damage. However, both vaccines induced chicken to generate similar level of neutralizing antibodies against C22, C22mut (R138K) and LaSota. These results suggest that the epitope mutation is insufficient to help NDV escaping neutralizing antibodies of vaccinated chicken, supporting that the merits of NDV matched vaccine are not totally related to humoral immunity.
疫苗被广泛用于预防新城疫病毒(NDV)。在免疫压力下,分离到了 F 和 HN 蛋白表位发生突变的 NDV,这表明疫苗的效率可能会降低,无法预防新出现的 NDV。然而,缺乏证据支持这些突变是否导致了 NDV 的抗原突变和免疫逃逸,这导致了一个争议,即匹配疫苗比不匹配疫苗更有效。在本研究中,从中国西藏的一个接种场分离到了一株基因型 VII 强毒 NDV 株(C22)。我们发现,该毒株与来自华东的 NDV 密切相关,但在 HN 蛋白的一个表位(DYIGGIGKE)中存在一个特定的突变(K138R)。这种突变可能改变 HN 蛋白茎-头部连接区氨基酸之间的相互作用,从而导致针对 C22 株的特异性抗体识别能力下降,但它并没有改变病毒的毒力和生长能力。然后,通过修饰 F 蛋白裂解位点,使 C22 株减弱,从而产生了匹配疫苗。与不匹配疫苗(LaSota)相比,这种匹配疫苗在抑制病毒脱落和组织损伤方面具有优势。然而,两种疫苗都能诱导鸡产生针对 C22、C22mut(R138K)和 LaSota 的相似水平的中和抗体。这些结果表明,表位突变不足以帮助 NDV 逃避接种鸡的中和抗体,这支持了 NDV 匹配疫苗的优点并不完全与体液免疫有关。