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Vaccination with virus-like particles protects mice from lethal infection of Rift Valley fever virus
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. (Swedish Defence Research Agency, Department of CBRN Defence and Security, SE-901 82 Umeå, Sweden)
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. (Swedish Defence Research Agency, Department of CBRN Defence and Security, SE-901 82 Umeå, Sweden)
Department of Virology, University of Freiburg, D-79008 Freiburg, Germany.
Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
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2009 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 385, no 2, 409-415 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 385, no 2, 409-415 p.
Keyword [en]
Rift Valley Fever virus
National Category
Infectious Medicine
URN: urn:nbn:se:umu:diva-21105DOI: 10.1016/j.virol.2008.12.012PubMedID: 19157482OAI: diva2:210601
Available from: 2009-04-02 Created: 2009-04-02 Last updated: 2011-10-14Bibliographically approved
In thesis
1. Rift Valley fever: development of diagnostics and vaccines
Open this publication in new window or tab >>Rift Valley fever: development of diagnostics and vaccines
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rift Valley Fever virus (RVFV) causes an infection with severe impact on animal and human health. The disease is endemic throughout almost the entire African continent and large regions of the Arabian Peninsula. During epidemics, high mortality is observed in animals, especially among cattle, goats, and sheep. In humans, the symptoms vary from a benign influenza-like disease to a life-threatening hemorrhagic fever. Due to the devastating effect on communities in endemic regions and the possibility of further spread of this virus, there is an imperative need to improve and develop control measurements against this emerging disease. Therefore, this thesis focuses on diagnostics and vaccines against RVFV.

RVFV infection kinetics was studied in a mouse model system by detection and quantification of viral genomes, using a developed quantitative real-time PCR (QRT-PCR) method. This novel QRT-PCR method proved to be reliable and serves as a supplement to standard diagnostics, direct virus isolation and serological methods. High levels of viral RNA were found in blood and liver samples from experimentally infected mice during the first days post infection. Thereafter the levels declined rapidly and dropped below detection limit approximately seven days post infection. The QRT-PCR technique was also used in a study aimed to improve diagnosis of RVFV from field samples collected on filter strips.

Today, the available RVFV vaccines are only approved for animal use and these vaccines have several shortcomings. Since RVFV is a highly pathogenic organism requiring bio-safety level 3 laboratories, two different none-replicating vaccine approaches have been applied and evaluated using a mouse model. A DNA based vaccine, administered via gene-gun, and the use of virus-like particles (VLP), by the intra-peritoneal route. RVFV specific and neutralising antibodies were raised with both vaccine approaches. However, VLP vaccination against Rift valley Fever proved to be more promising as a future vaccine, since higher titres of neutralising antibodies and improved survival rate were found upon a lethal RVFV challenge in mice.

In conclusion, a sensitive and specific method for quantifying RVFV infection and a promising vaccine candidate against RVFV were developed.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2010. 64 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1323
Rift Valley Fever, vaccines, diagnostics
National Category
Medical and Health Sciences Microbiology in the medical area
Research subject
Medical Virology; Infectious Diseases
urn:nbn:se:umu:diva-30676 (URN)978-91-7264-883-8 (ISBN)
Public defence
2010-02-05, Betula, byggnad 6M, 901 85 umeå universitet, NUS, 09:00 (English)
Available from: 2010-01-18 Created: 2010-01-12 Last updated: 2010-01-18Bibliographically approved

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