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Rabies-based vaccine induces potent immune responses against Nipah virus
npj Vaccines ( IF 6.9 ) Pub Date : 2019-04-15 , DOI: 10.1038/s41541-019-0109-5
Rohan Keshwara 1 , Thomas Shiels 1 , Elena Postnikova 2 , Drishya Kurup 1 , Christoph Wirblich 1 , Reed F Johnson 3 , Matthias J Schnell 1, 4
Affiliation  

Nipah Virus (NiV) is a re-emerging zoonotic pathogen in the genus Henipavirus of the Paramyxoviridae family of viruses. NiV is endemic to Bangladesh and Malaysia and is highly fatal to both livestock and humans (human case fatality rate = 74.5%). Currently, there is no approved vaccine against NiV on the market. The goal of this study was to use a recombinant RABV vector expressing NiV glycoprotein (NiV G) to develop a bivalent candidate vaccine against NiV disease and rabies virus (RABV) disease, which is also a significant health burden in the regions where NiV is endemic. The rabies vector is a well-established vaccine strain that lacks neurovirulence and can stably expresses foreign antigens that are immunogenic in various animal models. Mice inoculated intranasally with the live recombinant RABV/NiV vaccine (NIPARAB) showed no signs of disease. To test the immunogenicity of the vaccine candidate, groups of C57BL/6 mice were immunized intramuscularly with a single dose of live vaccine particles or two doses of chemically inactivated viral particles. Both vaccination groups showed NiV G-specific seroconversion, and the inactivated (INAC) vaccine group yielded higher titers of NiV G-specific antibodies. Furthermore, cross-reactivity of NiV G-specific immune sera against Hendra virus (HeV), was confirmed by immunofluorescence (IF) and indirect ELISA against soluble recombinant HeV glycoprotein (HeV G). Both live and killed vaccines induced neutralizing antibodies. These results indicate that NIPARAB may be used as a killed virus vaccine to protect humans against NiV and RABV, and possibly as a preventative measure against HeV as well.



中文翻译:


狂犬病疫苗可诱导针对尼帕病毒的有效免疫反应



尼帕病毒 (NiV) 是副粘病毒科亨尼帕病毒属中重新出现的人畜共患病原体。 NiV 是孟加拉国和马来西亚的地方病,对牲畜和人类均具有高度致命性(人类病死率 = 74.5%)。目前,市场上还没有批准的针对 NiV 的疫苗。本研究的目标是使用表达 NiV 糖蛋白 (NiV G) 的重组 RABV 载体来开发针对 NiV 疾病和狂犬病病毒 (RABV) 疾病的二价候选疫苗,这也是 NiV 流行地区的重大健康负担。狂犬病载体是一种成熟的疫苗株,缺乏神经毒力,可以稳定表达在各种动物模型中具有免疫原性的外源抗原。鼻内接种重组 RABV/NiV 活疫苗 (NIPARAB) 的小鼠没有表现出疾病迹象。为了测试候选疫苗的免疫原性,使用单剂活疫苗颗粒或两剂化学灭活病毒颗粒对 C57BL/6 小鼠组进行肌内免疫。两个疫苗接种组都显示出 NiV G 特异性血清转化,灭活 (INAC) 疫苗组产生了更高滴度的 NiV G 特异性抗体。此外,通过免疫荧光 (IF) 和针对可溶性重组 HeV 糖蛋白 (HeV G) 的间接 ELISA 证实了 NiV G 特异性免疫血清对亨德拉病毒 (HeV) 的交叉反应性。活疫苗和灭活疫苗都会诱导中和抗体。这些结果表明 NIPARAB 可用作灭活病毒疫苗,以保护人类免受 NiV 和 RABV 的侵害,也可能作为 HeV 的预防措施。

更新日期:2019-11-18
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