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

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.

Overlapping CD8 + and CD4 + T-cell epitopes identification for the progression of epitope-based peptide vaccine from nucleocapsid and glycoprotein of emerging Rift Valley fever virus using immunoinformatics approach

“…So, continuous outbreak of RVFV in different endemic and non-endemic regions highlight the exigent need for the development safe and effective vaccine. Among the seven RVFV proteins, the recent development focused on the viral nucleocapsid (N) and glycoprotein (G) based subunit vaccine that elicited robust virus neutralizing antibody responses in RVFV infected sheep (Faburay et al, 2014(Faburay et al, , 2016López-Gil et al, 2013;Pichlmair et al, 2010;van Vuren et al, 2007), and therefore, these two viral proteins are deliberated to be the promising target for effective RVFV vaccine design. Besides, several formalin-inactivated whole virus vaccine (Randall et al, 1964;Rusnak et al, 2011), liveattenuated vaccines (Clone 13 and MP-12) (Dungu et al, 2010;Muller et al, 1995), DNA vaccines Spik et al, 2006), Baculovirus expressed protein-based vaccines (Faburay et al, 2014;Schmaljohn et al, 1989), Virus like particles Näslund et al, 2009), and virus-vectored vaccines (Kortekaas et al, 2012;Wallace et al, 2006) were generated and tested on animals for the effectiveness, but these vaccines, except MP-12 did not get license due to the lack of potential safety and efficacy limitation (Ikegami, 2017).…”

Development and characterization of Rift Valley fever virus-like particles

“…Therefore, there is an urgent need for countermeasures to cope with RVFV that has been accidentally or intentionally introduced into non-endemic countries or regions. RVF vaccines used for animal vaccination in the endemic areas mainly include live-attenuated vaccines (Caplen et al, 1985;Muller et al, 1995;Kortekaas, 2014), inactivated vaccines (Randall et al, 1962;Rusnak et al, 2011), and genetically engineered vaccines (Kortekaas et al, , 2012López-Gil et al, 2013). These vaccines have inherent drawbacks, and no RVF vaccines for human use have been approved by the U.S. Food and Drug Administration.…”

Assessment of Immunogenicity and Efficacy of a Zika Vaccine Using Modified Vaccinia Ankara Virus as Carriers

“…The GeneArt prME plasmid was used as template to further generate the four ZIKV antigens (prME, prME ∆TM, Env, and Env ∆TM) as previously described ( [17]). ZIKV antigens were used to generate MVA viruses as previously described [24,25]. Briefly, the resulting antigen sequences were ligated into a shuttle vector, pMVA-GFP, which placed the open reading frame (ORF) under the control of the vaccinia p7.5 early/late promoter and also included GFP as a marker gene under the control of the vaccinia p11 late promoter.…”

“…Plaque picking was performed until the culture was free of parental virus, as determined by PCR. The recombinant viruses were plaque purified and then expanded in Doug-Foster-1 (DF-1) cells [24].…”