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Characterisation of immune responses and protective efficacy in mice after immunisation with Rift Valley Fever virus cDNA constructs
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. (Clas Ahlm)
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. (Clas Ahlm)
Smittskyddsinstitutet - Swedish Institute for Infectious Disease Control.
Institut Pasteur, Paris, Frankrike.
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2009 (English)In: Virology journal, ISSN 1743-422X, Vol. 6, 6- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Affecting both livestock and humans, Rift Valley Fever is considered as one of the most important viral zoonoses in Africa. However, no licensed vaccines or effective treatments are yet available for human use. Naked DNA vaccines are an interesting approach since the virus is highly infectious and existing attenuated Rift Valley Fever virus vaccine strains display adverse effects in animal trials. In this study, gene-gun immunisations with cDNA encoding structural proteins of the Rift Valley Fever virus were evaluated in mice. The induced immune responses were analysed for the ability to protect mice against virus challenge. RESULTS: Immunisation with cDNA encoding the nucleocapsid protein induced strong humoral and lymphocyte proliferative immune responses, and virus neutralising antibodies were acquired after vaccination with cDNA encoding the glycoproteins. Even though complete protection was not achieved by genetic immunisation, four out of eight, and five out of eight mice vaccinated with cDNA encoding the nucleocapsid protein or the glycoproteins, respectively, displayed no clinical signs of infection after challenge. In contrast, all fourteen control animals displayed clinical manifestations of Rift Valley Fever after challenge. CONCLUSION: The appearance of Rift Valley Fever associated clinical signs were significantly decreased among the DNA vaccinated mice and further adjustment of this strategy may result in full protection against Rift Valley Fever.

Place, publisher, year, edition, pages
2009. Vol. 6, 6- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-30671DOI: 10.1186/1743-422X-6-6PubMedID: 19149901OAI: diva2:285524
Available from: 2010-01-12 Created: 2010-01-12 Last updated: 2012-06-05Bibliographically 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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