Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, United States of America.
The Jenner Institute, University of Oxford, Oxford, United Kingdom.
PLoS Negl Trop Dis. 2019 Jun 6;13(6):e0007462. doi: 10.1371/journal.pntd.0007462. eCollection 2019 Jun.
Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiVB, a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiVB also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiVB also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiVB vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiVB is a suitable candidate for further NiV vaccine pre-clinical development.
尼帕病毒(NiV)是一种高致病性的新兴病毒,在东南亚引发疫情。目前,尚无经过批准和许可的疫苗或抗病毒药物。在这里,我们研究了 ChAdOx1 NiVB(一种基于猴腺病毒的疫苗,编码 NiV 糖蛋白[G]孟加拉国株)在叙利亚仓鼠中的功效。仅进行初免以及初免-加强免疫接种均可对致命性 NiV 孟加拉国株挑战实现均匀保护:所有动物均存活下来,我们未能在口腔拭子、肺部或脑组织中发现感染性病毒。此外,肺部也没有观察到病理损伤。单次接种 ChAdOx1 NiVB 还可预防同源性 NiV 马来西亚株的挑战导致的疾病和死亡。虽然我们未能在接受异源株挑战的动物的拭子或组织中检测到感染性病毒,但通过原位杂交可在肺部组织中发现极少量的病毒 RNA。单次接种 ChAdOx1 NiVB 还对亨德拉病毒提供了部分保护,而 ChAdOx1 NiVB 接种产生的抗体的被动转移部分保护了叙利亚仓鼠免受 NiV 孟加拉国株的侵害。根据这些数据,我们得出结论,ChAdOx1 NiVB 是进一步进行 NiV 疫苗临床前开发的合适候选者。