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用病毒样颗粒进行疫苗接种可保护小鼠免受裂谷热病毒的致死性感染。

Vaccination with virus-like particles protects mice from lethal infection of Rift Valley Fever Virus.

作者信息

Näslund Jonas, Lagerqvist Nina, Habjan Matthias, Lundkvist Ake, Evander Magnus, Ahlm Clas, Weber Friedemann, Bucht Göran

机构信息

Swedish Defence Research Agency, Department of CBRN Defence and Security, SE-901 82 Umeå, Sweden.

出版信息

Virology. 2009 Mar 15;385(2):409-15. doi: 10.1016/j.virol.2008.12.012. Epub 2009 Jan 20.

DOI:10.1016/j.virol.2008.12.012
PMID:19157482
Abstract

Rift Valley Fever virus (RVFV) regularly accounts for severe and often lethal outbreaks among livestock and humans in Africa. Safe and effective veterinarian and human vaccines are highly needed. We present evidence that administration of RVF virus-like particles (VLPs) induces protective immunity in mice. In an accompanying paper, (Habjan, M., Penski, N., Wagner, V., Spiegel, M., Overby, A.K., Kochs, G., Huiskonen, J., Weber, F., 2009. Efficient production of Rift Valley fever virus-like particles: the antiviral protein MxA can inhibit primary transcription of Bunyaviruses. Virology 385, 400-408) we report the production of these VLPs in mammalian cells. After three subsequent immunizations with 1x10(6) VLPs/dose, high titers of virus-neutralizing antibodies were detected; 11 out of 12 mice were protected from challenge and only 1 out of 12 mice survived infection in the control groups. VLP vaccination efficiently suppressed replication of the challenge virus, whereas in the control animals high RNA levels and increasing antibody titers against the nucleocapsid protein indicated extensive viral replication. Our study demonstrates that the RVF VLPs are highly immunogenic and confer protection against RVFV infection in mice. In the test groups, the vaccinated mice did not exhibit any side effects, and the lack of anti-nucleocapsid protein antibodies serologically distinguished vaccinated animals from experimentally infected animals.

摘要

裂谷热病毒(RVFV)在非洲经常导致家畜和人类中出现严重且往往致命的疫情。非常需要安全有效的兽用和人用疫苗。我们提供的证据表明,给予裂谷热病毒样颗粒(VLPs)可在小鼠中诱导保护性免疫。在一篇配套论文中(Habjan, M., Penski, N., Wagner, V., Spiegel, M., Overby, A.K., Kochs, G., Huiskonen, J., Weber, F., 2009. 高效生产裂谷热病毒样颗粒:抗病毒蛋白MxA可抑制布尼亚病毒的初级转录。病毒学385, 400 - 408),我们报告了这些VLPs在哺乳动物细胞中的生产情况。用1×10⁶个VLPs/剂量进行三次后续免疫后,检测到高滴度的病毒中和抗体;12只小鼠中有11只受到保护免受攻击,而对照组中12只小鼠只有1只在感染后存活。VLP疫苗接种有效抑制了攻击病毒的复制,而在对照动物中,高RNA水平和针对核衣壳蛋白的抗体滴度增加表明病毒大量复制。我们的研究表明,裂谷热VLPs具有高度免疫原性,并能在小鼠中提供针对RVFV感染的保护。在试验组中,接种疫苗的小鼠未表现出任何副作用,并且血清学上缺乏抗核衣壳蛋白抗体可将接种疫苗的动物与实验感染的动物区分开来。

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