Development of an Effective and Stable Genotype-Matched Live Attenuated Newcastle Disease Virus Vaccine Based on a Novel Naturally Recombinant Malaysian Isolate Using Reverse Genetics
Development of an Effective and Stable Genotype-Matched Live Attenuated Newcastle Disease Virus Vaccine Based on a Novel Naturally Recombinant Malaysian Isolate Using Reverse Genetics
复制标题
DOI：
10.3390/vaccines8020270
复制
发表时间：
2020-06-01
期刊：
影响因子：
7.8
通讯作者：
Omar, Abdul Rahman
中科院分区：
文献类型：
--
作者：
Bello, Muhammad Bashir;Mahamud, Siti Nor Azizah;Omar, Abdul Rahman
基因型VII纽卡斯尔病病毒与全球家禽业的巨大经济损失有关。尽管大量使用疫苗，但即使在接种疫苗的家禽养殖场中，这些病毒引起的疾病暴发仍经常发生。目前疫苗保护效力欠佳的一个重要因素是流行毒株和疫苗毒株之间的遗传错配。因此，在本研究中，一个有效的和稳定的基因型匹配的活减毒纽卡斯尔病病毒（NDV）疫苗的基础上，利用反向遗传学，最近分离的强毒天然重组NDV IBS 025/13马来西亚株。首先，将编码病毒融合蛋白（F）切割位点的序列从强毒多碱基（RRQKRF）基序计算机修饰为无毒单碱基（GRQGRL）基序。然后化学合成整个修饰序列并插入pOLTV 5转录载体用于病毒拯救。重组病毒mIBS 025被成功回收，并根据OIE推荐的致病性评估指标显示高度减毒。此外，该病毒被证明保持稳定减毒，并保留了无毒monoblavirus F裂解位点后，在特定病原体的无胚蛋和12代在一日龄鸡连续传代15次。更重要的是，重组病毒诱导了显着更高的血凝抑制抗体滴度比LaSota，虽然这两种疫苗完全保护鸡对基因型VII NDV诱导的死亡率和发病率。最后，与LaSota疫苗相比，mIBS 025显示出显著减少了攻击的基因型VII病毒的泄殖腔和口咽脱落的持续时间和数量。这些发现共同表明，mIBS 025提供了比LaSota更好的保护效力，因此可以用作针对基因型VII NDV毒株的有希望的候选疫苗。
Genotype VII Newcastle disease viruses are associated with huge economic losses in the global poultry industry. Despite the intensive applications of vaccines, disease outbreaks caused by those viruses continue to occur frequently even among the vaccinated poultry farms. An important factor in the suboptimal protective efficacy of the current vaccines is the genetic mismatch between the prevalent strains and the vaccine strains. Therefore, in the present study, an effective and stable genotype-matched live attenuated Newcastle disease virus (NDV) vaccine was developed using reverse genetics, based on a recently isolated virulent naturally recombinant NDV IBS025/13 Malaysian strain. First of all, the sequence encoding the fusion protein (F) cleavage site of the virus was modified in silico from virulent polybasic (RRQKRF) to avirulent monobasic (GRQGRL) motif. The entire modified sequence was then chemically synthesized and inserted into pOLTV5 transcription vector for virus rescue. A recombinant virus termed mIBS025 was successfully recovered and shown to be highly attenuated based on OIE recommended pathogenicity assessment indices. Furthermore, the virus was shown to remain stably attenuated and retain the avirulent monobasic F cleavage site after 15 consecutive passages in specific-pathogen-free embryonated eggs and 12 passages in one-day-old chicks. More so, the recombinant virus induced a significantly higher hemagglutination inhibition antibody titre than LaSota although both vaccines fully protected chicken against genotype VII NDV induced mortality and morbidity. Finally, mIBS025 was shown to significantly reduce both the duration and quantity of cloacal and oropharyngeal shedding of the challenged genotype VII virus compared to the LaSota vaccine. These findings collectively indicate that mIBS025 provides a better protective efficacy than LaSota and therefore can be used as a promising vaccine candidate against genotype VII NDV strains.