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

被引:79
作者
Naslund, Jonas [2 ,3 ,4 ]
Lagerqvist, Nina [2 ,3 ,5 ]
Habjan, Matthias [1 ]
Lundkvist, Ake [5 ]
Evander, Magnus [4 ]
Ahlm, Clas [3 ]
Weber, Friedemann [1 ]
Bucht, Goran [2 ,6 ]
机构
[1] Univ Freiburg, Dept Virol, D-79008 Freiburg, Germany
[2] Swedish Def Res Agcy, Dept CBRN Def & Secur, SE-90182 Umea, Sweden
[3] Umea Univ, Dept Clin Microbiol, Div Infect Dis, SE-90185 Umea, Sweden
[4] Umea Univ, Dept Clin Microbiol, Div Virol, SE-90185 Umea, Sweden
[5] Swedish Inst Infect Dis Control, SE-17182 Solna, Sweden
[6] Environm Hlth Inst, Natl Environm Agcy, Singapore 138667, Singapore
基金
瑞典研究理事会;
关键词
Rift Valley Fever; Mouse model; Virus-like particle; Vaccine; Challenge; HEPATITIS-B VACCINE; IMMUNE-RESPONSES; FOLLOW-UP; EXPRESSION; PROTEINS; EFFICACY; TRIAL; L1; RESCUE; HUMANS;
D O I
10.1016/j.virol.2008.12.012
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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, E, 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 1 x 10(6) VLPs/dose, high titers of virus-neutralizing antibodies were detected; 11 out of 12 mice were protected from challenge and only I out of 42 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. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:409 / 415
页数:7
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