Abstract
BackgroundRift Valley fever virus (RVFV) is a mosquito-borne pathogen causing an important disease in ruminants often transmitted to humans after epizootic outbreaks in African and Arabian countries. To help combat the spread of the disease, prophylactic measures need to be developed and/or improved.Methodology/Principal FindingsIn this work, we evaluated the immunogenicity and protective efficacy of recombinant plasmid DNA and modified vaccinia virus Ankara (rMVA) vectored vaccines against Rift Valley fever in mice. These recombinant vaccines encoded either of two components of the Rift Valley fever virus: the viral glycoproteins (Gn/Gc) or the nucleoprotein (N). Following lethal challenge with live RVFV, mice immunized with a single dose of the rMVA-Gn/Gc vaccine showed no viraemia or clinical manifestation of disease, but mounted RVFV neutralizing antibodies and glycoprotein specific CD8+ T-cell responses. Neither DNA-Gn/Gc alone nor a heterologous prime-boost immunization schedule (DNA-Gn/Gc followed by rMVAGn/Gc) was better than the single rMVA-Gn/Gc immunization schedule with regards to protective efficacy. However, the rMVA-Gn/Gc vaccine failed to protect IFNAR−/− mice upon lethal RVFV challenge suggesting a role for innate responses in protection against RVFV. Despite induction of high titer antibodies against the RVFV nucleoprotein, the rMVA-N vaccine, whether in homologous or heterologous prime-boost schedules with the corresponding recombinant DNA vaccine, only conferred partial protection to RVFV challenge.Conclusions/SignificanceGiven the excellent safety profile of rMVA based vaccines in humans and animals, our data supports further development of rMVA-Gn/Gc as a vaccine strategy that can be used for the prevention of Rift Valley fever in both humans and livestock.
Highlights
Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing periodic outbreaks of disease in livestock as well as numerous human infections and fatalities in many African countries
Rift Valley fever (RVF) is an important disease of ruminants that affects most African and Arabian Peninsula countries where domestic livestock is the basis for subsistence in rural areas
A number of specific immune CD8+-T cells could be activated in the presence of at least three different glycoprotein epitopes
Summary
Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing periodic outbreaks of disease in livestock as well as numerous human infections and fatalities in many African countries (reviewed in [1]). After extensive mainland outbreaks [3,4,5,6,7,8] the disease has since appeared in the Arabian Peninsula [9] and several Indian Ocean islands [10,11,12,13] This ability to cross geographical barriers raises concerns of potential spread to RVFV-naive areas [14]. Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing an important disease in ruminants often transmitted to humans after epizootic outbreaks in African and Arabian countries. To help combat the spread of the disease, prophylactic measures need to be developed and/or improved
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