A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: In 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/SIGNIFICANCE: Given 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.

European ring trial to evaluate ELISAs for the diagnosis of infection with Rift Valley fever virus.

A ring trial was organized to evaluate Rift Valley fever virus (RVFV) ELISAs by European laboratories. A total of five ELISAs, two of which specific for IgM antibodies, were evaluated by six participants. Sera were derived from cattle or sheep and originated from either a RVFV endemic area, a RVFV-free area or from experimental infection studies. Cohen's kappa analysis showed higher than 90% agreement of two commercially available ELISAs with the virus neutralization test, suggesting that primary screening as well as serological confirmation using these ELISAs is feasible. More extensive validations with sera of known IgM status are, however, required to determine agreement between IgM ELISAs.

Protection against lethal Rift Valley fever virus (RVFV) infection in transgenic IFNAR(-/-) mice induced by different DNA vaccination regimens.

In this work, plasmid constructs encoding two different M segment ORFs, as well as the nucleoprotein N, have been used in different vaccination regimes to test protection against a RVFV-MP12 virus challenge in a transgenic mouse model with impaired interferon type I response (IFNAR(-/-)). We obtained dose dependent protection in animals immunized with a construct encoding both mature glycoproteins (pCMV-M4), whereas only partial protection in animals vaccinated with either N construct (pCMV-N) or a combination of both plasmids (pCMV-M4+pCMV-N). The protection elicited by the expression of the mature glycoproteins could be directly related to the induction of neutralizing antibodies against them. Interestingly, the combination of both vaccine constructs induced specific lymphoblast proliferation upon stimulation with a recombinant nucleoprotein.