Abstract

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suitable for use in livestock or humans outside endemic areas. Here we report the evaluation of the efficacy of a recombinant subunit vaccine based on the RVFV Gn and Gc glycoproteins. In a previous study, the vaccine elicited strong virus neutralizing antibody responses in sheep and was DIVA (differentiating naturally infected from vaccinated animals) compatible. In the current efficacy study, a group of sheep (n = 5) was vaccinated subcutaneously with the glycoprotein-based subunit vaccine candidate and then subjected to heterologous challenge with the virulent Kenya-128B-15 RVFV strain. The vaccine elicited high virus neutralizing antibody titers and conferred complete protection in all vaccinated sheep, as evidenced by prevention of viremia, fever and absence of RVFV-associated histopathological lesions. We conclude that the subunit vaccine platform represents a promising strategy for the prevention and control of RVFV infections in susceptible hosts.

Highlights

  • The presence of competent vectors in non-endemic areas presents significant risk of introduction and further spread of RVFV3–5

  • The occurrence of Rift Valley fever virus (RVFV) outbreaks outside the African continent in 2000 in the Arabian Peninsula demonstrated the potential for the virus to spread to non-endemic areas

  • We developed and evaluated the efficacy of a recombinant subunit vaccine candidate composed of RVFV surface glycoproteins, Gn and Gc, adjuvanted with montanide ISA25 VG, in a ruminant model

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Summary

Introduction

The presence of competent vectors in non-endemic areas presents significant risk of introduction and further spread of RVFV3–5. A natural attenuated isolate, Clone 13, from a benign RVF case in the Central African Republic[11], and a chemically attenuated virus, MP12, derived from ZH548, an Egyptian wild-type isolate[12], have been evaluated for efficacy[13,14,15] These attenuated vaccines have shown promising results[16], safety issues associated with their use in non-endemic regions remain a major concern[17]. Another drawback of the live-attenuated RVFV vaccines is that they do not allow for differentiation of www.nature.com/scientificreports/. The current work is a logical continuation of this work aimed at evaluating the efficacy of the recombinant Gn/Gc subunit vaccine candidate to protect against heterologous virus challenge in sheep

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