Attenuated Rift Valley Fever Virus:
human and veterinary vaccine applications
Description of invention:
Rift Valley fever virus (RVFV) is an arbovirus of the Bunyaviridae family, causing devastating disease outbreaks in livestock (including cattle, buffalo, sheep and goats), which kill tens of thousands of animals. Rift Valley fever is most commonly found in livestock-raising regions of Africa, though the most recent outbreak (Sept. 2000) occurred in Saudi Arabia and Yemen. Human cases of the disease have been reported since the late 1970’s. Approximately 1% of infected people die of the disease. Death rates are much higher for infected animals. Moreover, the fatality rate for fetuses in pregnant livestock is 100%, and the fatality rate for newborn lambs is 90%.
RVFV is transmitted to humans primarily by infected Aedes or Culex mosquitoes and by direct contact with the blood or body fluids of infected animals. Vaccines for veterinary use are available, but are known to cause birth defects and abortions in sheep and provide only low-level protection in cattle. No effective vaccine or antiviral medication is approved for use in humans.
A human live attenuated vaccine, MP-12, has demonstrated good protection rates in animals, with attenuation markers in the three constitutive viral genomic segments (L, M and S). Unfortunately, it also gives rise to significant pathogenic side effects in cattle. A distinct, naturally-derived variant, Clone 13, includes an attenuation in the S segment and expresses good immunogenicity. However, for biosafety reasons, a vaccine including attenuation markers in each of the three genomic segments is more desirable, as it would minimize the rearrangement risk with wild type pathogenic clones. Such a vaccine candidate has been produced by researchers at the Institut Pasteur. As shown by ELISA analysis, this new clone induces an antibody response superior to the one induced by clones MP12 and C13 alone. Protection obtained was similar to the one achieved with the MP12 clone, but the new clone showed no pathogenic effects and no virulence in mice. This clone therefore appears to be a promising candidate for vaccine development in both animals and humans.
Recent pertinent publications
Vialat P, Billecocq A, Kohl A, Bouloy M. J Virol 2000 Feb;74(3):1538-43
French patent application filed March 24, 2000
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