Abstract
Many ruminant diseases of viral aetiology can be effectively prevented using appropriate vaccination measures. For diseases such as Rift Valley fever (RVF) the long inter-epizootic periods make routine vaccination programs unfeasible. Coupling RVF prophylaxis with seasonal vaccination programmes by means of multivalent vaccine platforms would help to reduce the risk of new RVF outbreaks. In this work we generated recombinant attenuated Rift Valley fever viruses (RVFVs) encoding in place of the virulence factor NSs either the VP2 capsid protein or a truncated form of the non-structural NS1 protein of bluetongue virus serotype 4 (BTV-4). The recombinant viruses were able to carry and express the heterologous BTV genes upon consecutive passages in cell cultures. In murine models, a single immunization was sufficient to protect mice upon RVFV challenge and to elicit a specific immune response against BTV-4 antigens that was fully protective after a BTV-4 boost. In sheep, a natural host for RVFV and BTV, both vaccines proved immunogenic although conferred only partial protection after a virulent BTV-4 reassortant Morocco strain challenge. Though additional optimization will be needed to improve the efficacy data against BTV in sheep, our findings warrant further developments of attenuated RVFV as a dual vaccine platform carrying heterologous immune relevant antigens for ruminant diseases in RVF risk areas.
Highlights
Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing severe disease outbreaks affecting humans and livestock in sub-Saharan Africa, Egypt, Yemen, Saudi Arabia and the Indian Ocean islands [1]
In this work we report the generation of attenuated Rift Valley fever virus (RVFV) that express vaccine antigens of bluetongue virus (BTV) instead of the virulence factor NSs
The recombinant viruses were able to induce protective immune responses against both RVFV and BTV when administered as vaccines in mice and sheep respectively
Summary
Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing severe disease outbreaks affecting humans and livestock in sub-Saharan Africa, Egypt, Yemen, Saudi Arabia and the Indian Ocean islands [1]. RVFV belongs to the Phlebovirus genus from the Phenuiviridae family, Order Bunyavirales It is an enveloped, single-stranded RNA virus with a segmented genome of negative and ambisense polarity [4]. Natural NSs deletion mutants were found with an attenuated or avirulent phenotype [9] due to the presence of an activated IFN system [7,8] One of these NSs deletion mutants, Clone 13, constitutes a live attenuated vaccine derivative considered as a promising control measure in African countries. In spite of the availability of effective RVF vaccines in Africa, the sporadic, often unpredictable, RVF outbreaks after long inter-epizootic periods makes annual vaccination programs difficult to be established. Many ruminant diseases of viral aetiology can be effectively prevented using appropriate vaccination measures For diseases such as Rift Valley fever (RVF) the long inter-epizootic periods make routine vaccination programs unfeasible. Coupling RVF prophylaxis with seasonal vaccination programmes by means of multivalent vaccine platforms would help to reduce the risk of new RVF outbreaks
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