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Recombinant Measles Virus Vaccine Expressing the Nipah Virus Glycoprotein Protects against Lethal Nipah Virus Challenge

机译:重组麻疹病毒疫苗表达尼帕病毒糖蛋白防止致命尼帕病毒挑战

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摘要

Nipah virus (NiV) is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G). Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi). Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.
机译:Nipah病毒(NiV)是Henipavirus的成员,该病毒于1998年在马来西亚出现。在猪中,感染导致主要为非致死性呼吸道疾病。但是,人类感染导致100多人死亡。 Nipah病毒继续在孟加拉国和印度重新出现,人与人之间的传播出现在爆发中。尽管已报道了许多NiV疫苗研究,但目前尚无许可用于人类的疫苗或治疗方法。在这项研究中,我们开发了一种表达NiV包膜糖蛋白(rMV-HL-G和rMV-Ed-G)的重组麻疹病毒(rMV)疫苗。完全免疫接种的仓鼠可以抵抗NiV攻击,而未接种的对照仓鼠的死亡率为90%。我们在非人类灵长类动物模型非洲绿猴中试用了我们的疫苗。腹膜内感染NiV后,猴子表现出几种疾病的临床体征,包括严重的抑郁症,移动能力下降和食物摄入减少,并在感染后7天死亡(dpi)。鼻内和口腔接种在猴子中引起相似的临床疾病,在9 dpi左右很明显,并在14 dpi左右导致濒死阶段。用rMV-Ed-G皮下免疫的两只猴子在用NiV攻击后在安乐死之前没有临床疾病。在从接种过的猴子收集的任何器官样本中均未检测到病毒RNA,并且在组织病理学检查中未发现病理变化。根据我们的发现,我们建议rMV-NiV-G是用于人类的合适NiV疫苗候选者。

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