Shahar Ehud, Haddas Ruth, Goldenberg Dana, Lublin Avishai, Bloch Itai, Bachner Hinenzon Noa, Pitcovski Jacob
a MIGAL - Galilee Technology Center , Kiryat Shmona , Israel.
b Division of Avian Diseases , Kimron Veterinary Institute , Bet-Dagan , Israel.
Avian Pathol. 2018 Oct;47(5):467-478. doi: 10.1080/03079457.2018.1488240. Epub 2018 Jul 5.
Newcastle disease virus (NDV) is a major cause of infectious mortality and morbidity in poultry worldwide. It is an enveloped virus with two outer-membrane proteins-haemagglutinin-neuraminidase (HN) and fusion protein (F)-that induce neutralizing antibodies. All NDV strains belong to one serotype. Yet, NDV vaccines, derived from genotype II, do not fully prevent infection or shedding of viruses from other genotypes. The aim of this study was to test if an updated vaccine is required. For this purpose, NDVs isolated from infected, albeit heavily vaccinated, flocks were genetically and immunologically characterized. Amino acid differences in F and HN protein sequences were identified between the vaccine strain and each of the isolates, some specifically at the neutralization sites. Whereas all tested isolates showed similar haemagglutination-inhibition (HI) titres, 100-100,000 times higher antibody-to-virus ratios were needed to neutralize viral propagation in embryos by the field isolates versus the vaccine strain. As a result, a model and an equation were developed to explain the phenomenon of escape in one-serotype viruses and to calculate the HI values needed for protection, depending on variation rate at key positions. In conclusion, to confer full protection against NDVs that differ from the vaccine strain at the neutralizing epitopes, very high levels of antibodies should be raised and maintained to compensate for the reduction in the number of effective epitopes; alternatively, an adjusted attenuated vaccine should be developed-a task made possible in the current era of reverse vaccinology.
新城疫病毒（NDV）是全球家禽感染性死亡和发病的主要原因。它是一种包膜病毒，具有两种外膜蛋白——血凝素神经氨酸酶（HN）和融合蛋白（F），可诱导中和抗体。所有NDV毒株都属于一个血清型。然而，源自基因型II的NDV疫苗并不能完全预防其他基因型病毒的感染或病毒排出。本研究的目的是测试是否需要更新疫苗。为此，对从尽管大量接种疫苗但仍受感染的鸡群中分离出的NDV进行了基因和免疫学特征分析。在疫苗株与每个分离株之间鉴定出F和HN蛋白序列中的氨基酸差异，有些差异特别出现在中和位点。尽管所有测试分离株的血凝抑制（HI）效价相似，但与疫苗株相比，需要高100 - 100,000倍的抗体与病毒比率才能中和野毒株在胚胎中的病毒增殖。结果，开发了一个模型和一个方程式来解释单血清型病毒的逃逸现象，并根据关键位置的变异率计算保护所需的HI值。总之，如果要对在中和表位上与疫苗株不同的NDV提供全面保护，应产生并维持非常高水平的抗体，以补偿有效表位数量的减少；或者，应开发一种经过调整的减毒疫苗——这在当前的反向疫苗学时代是一项可行的任务。
