The Smithburn virus vaccine is suggested to induce lifelong protection, but has retained the ability to induce abortions and teratogenic effects in livestock [9,10]. The inactivated virus vaccines are safe, but less immunogenic and require annual booster vaccinations [11]. Previously, two vaccine candidates have been proposed and tested STI571 for their safety and efficacy in animal trials: a naturally attenuated RVFV isolate from a benign human case in the Central African Republic, Clone 13 [12] and a human virus isolate of RVFV attenuated in cell culture by 5-fluorouracil treatment, MP12 [13,14]. Although Clone 13 and MP12 were shown to be safe and immunogenic in mice and in cattle and sheep, respectively [12], the MP12 vaccine was found teratogenic for pregnant sheep if used during the first trimester [15].
In addition to the adverse effects previously shown for attenuated RVF vaccines, there are considerable safety concerns regarding viral vaccines based on highly pathogenic organisms due to the risk for exposure or escape of live agents during the manufacturing process. In addition, there is also a risk of insufficient inactivation or emergence of revertants, when large quantities of virulent virus strains are handled. Because of these shortcomings, new RVF vaccine strategies ought to be considered. Genetic immunisation is an attractive alternative, since the antigens are produced by the host cells and the presentation resembles natural infections by intracellular parasites. It is also cost-effective and circumvents the need for elevated biosafety level facilities [16].
Genetic vaccines are also less vulnerable to elevated temperatures during storage and transportation, which are important factors when performing vaccinations in developing countries [17]. These characteristics make DNA vaccines uniquely suited for vaccine production against highly pathogenic organisms, such as RVFV [18,19]. The RVFV is a three segmented negative stranded RNA virus. The (L)arge segment encodes a RNA dependent RNA polymerase and the (M)edium segment encodes two glycoproteins (GN and GC), a 78 kDa protein as well as a non-structural protein (NSm). The (S)mall segment encodes a non-structural protein (NSs) and the immunogenic and highly expressed nucleocapsid protein (N) [3]. Despite an abundance of the N protein in the virus and in the infected cell, this protein is not generally associated with protective immunity.
However, a recent study has shown that a proportion Cilengitide of mice inoculated with purified RVFV N proteins were protected against virus challenge [20]. Although antibodies targeting the RVFV glycoproteins are recognized for their protective properties [21] contradictory results regarding the level of protection after DNA vaccination have been presented [20,22,23].
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