Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge.
Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge.
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DOI：
10.1371/journal.pone.0058414
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kai C
中科院分区：
文献类型：
--
作者：
Yoneda M;Georges-Courbot MC;Ikeda F;Ishii M;Nagata N;Jacquot F;Raoul H;Sato H;Kai C
尼帕病毒（NiV）是亨尼帕病毒属的成员，于1998年在马来西亚出现。在猪中，感染主要导致非致命性呼吸道疾病;然而，人类感染导致100多人死亡。尼帕病毒继续在孟加拉国和印度重新出现，在疫情中出现了人与人之间的传播。尽管已经报道了一些NiV疫苗研究，但目前还没有疫苗或治疗方法被许可用于人类。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。接种疫苗的仓鼠对NiV攻击完全保护，而未接种疫苗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色猴中试验了我们的疫苗。在腹膜内感染NiV后，猴显示出疾病的几种临床体征，包括严重抑郁、移动能力降低和食物摄取减少，并在感染后7天（dpi）死亡。鼻内和经口接种在猴中诱导了相似的临床疾病，在9 dpi左右明显，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攻击后安乐死之前未显示临床疾病。从接种疫苗的猴中采集的任何器官样品均未检出病毒RNA，组织病理学检查未发现任何病理变化。根据我们的研究结果，我们提出rMV-NiV-G是用于人类的合适的NiV疫苗候选物。
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.
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影响因子：
11.8
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