Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
PLoS One. 2013;8(3):e58414. doi: 10.1371/journal.pone.0058414. Epub 2013 Mar 14.
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.
亨德拉病毒（NiV）是亨尼帕病毒属的成员，于 1998 年在马来西亚出现。在猪中，感染导致主要是非致命性的呼吸道疾病；然而，人类感染导致超过 100 人死亡。尼帕病毒继续在孟加拉国和印度重新出现，并且在疫情中出现了人际传播。尽管已经报道了许多尼帕病毒疫苗研究，但目前没有针对人类使用的许可疫苗或治疗方法。在这项研究中，我们开发了一种表达尼帕病毒包膜糖蛋白的重组麻疹病毒（rMV）疫苗（rMV-HL-G 和 rMV-Ed-G）。接种的仓鼠完全免受尼帕病毒的挑战，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（非洲绿猴）中试用了我们的疫苗。感染尼帕病毒后，猴子表现出几种疾病的临床症状，包括严重抑郁、运动能力下降和食物摄入减少，并在感染后 7 天死亡（dpi）。腹腔内和口服接种会在猴子中引起类似的临床疾病，在 9dpi 左右明显，并在 14dpi 左右导致濒死阶段。两只皮下接种 rMV-Ed-G 的猴子在接受尼帕病毒挑战后安乐死之前没有出现临床疾病。从接种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任何病理变化。根据我们的发现，我们提出 rMV-NiV-G 是一种适合人类使用的尼帕病毒疫苗候选物。
