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A protective bivalent vaccine against Rift Valley fever and bluetongue.

ABSTRACT: Rift Valley fever (RVF) and bluetongue (BT) are two important ruminant diseases transmitted by arthropods. Both viruses have shown important geographic spread leading to endemicity of BT virus (BTV) in Africa and Europe. In this work, we report a dual vaccine that simultaneously induces protective immune responses against BTV and RVFV based on modified vaccinia Ankara virus (MVA) expressing BTV proteins VP2, NS1, or a truncated form of NS1 (NS1-Nt), and RVFV Gn and Gc glycoproteins. IFNAR^(-/-) mice immunized with two doses of MVA-GnGc-VP2 developed a significant neutralizing antibody response against BTV-4 and RVFV. Furthermore, the homologous prime-boost immunization with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt triggered neutralizing antibodies against RVFV and NS1-specific cytotoxic CD8+ T cells in mice. Moreover, all mice immunized with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt remained healthy after lethal challenge with RVFV or BTV-4. The homologous prime-boost vaccination with MVA-GnGc-NS1, which was the best immunization strategy observed in mice, was assayed in sheep. Clinical signs and viremia were absent or highly reduced in vaccinated sheep after challenge with BTV-4 or RVFV. These results indicate that MVA-GnGc-NS1 vaccination elicits immune protection against RVFV and BTV in sheep.

SUBMITTER: Calvo-Pinilla E

PROVIDER: S-EPMC7393076 | biostudies-literature |

REPOSITORIES: biostudies-literature

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A Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Confers Full Protection against Rift Valley Fever Challenge in Sheep.

Project description: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.

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Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever.

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Correlative gene expression to protective seroconversion in Rift Valley Fever vaccinates

Project description:Rift Valley Fever Virus (RVFV), a negative-stranded RNA virus, is the etiological agent of the vector-borne zoonotic disease, Rift Valley Fever (RVF). In both humans and livestock, protective immunity can be achieved through vaccination. Earlier and more recent vaccine trials in cattle and sheep demonstrated a strong neutralizing antibody and total IgG response induced by the RVFV vaccine, MP-12. From previous work, protective immunity in sheep and cattle vaccinates normally occurs from 7 to 21 days after inoculation with MP-12. While the serology and protective response induced by MP-12 has been studied, little attention has been paid to the underlying molecular and genetic events occurring prior to the serologic immune response. To address this, we isolated RNA from whole blood from vaccinates over a time course of 21 days before and after inoculation during a recent vaccine trial with MP-12. This RNA time course was deeply sequenced by RNASeq and bioinformatically analyzed. Our results revealed time-dependent activation or repression of numerous gene ontologies and pathways related to immune response and regulation. Additional analyses identified a correlative relationship between specific genes related to immune activity and protective immunity prior to serologic detection of antibody response. These data provide an important proof of concept for identifying molecular and genetic components underlying the immune response to vaccination and protection prior to serologic detection.

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An Overview of Rift Valley Fever Vaccine Development Strategies.

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MAVS mediates a protective immune response in the brain to Rift Valley fever virus

Project description:Rift Valley fever virus causes severe disease in humans and livestock and in some cases can be fatal. There is concern about the use of Rift Valley fever virus as a bioweapon since it can be transmitted through the air, and there are no vaccines or antiviral treatments. Airborne transmission of the virus causes severe inflammation of the brain, yet little is known about the immune response against the virus in this organ. Here, we investigated the immune response in the brain to Rift Valley fever virus following intranasal infection. We determined that microglia, the resident immune cells of the brain, initiate a robust response to Rift Valley fever virus infection and identified a key immune pathway that is critical for the ability of microglia to respond to infection. When this immune pathway is rendered non-functional, mice have a dysregulated response to infection in the brain.

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Rift Valley fever virus

Project description:Rift Valley Fever Virus genome from Mayotte, Indian Ocean

| PRJNA517473 | ENA

Rift Valley fever virus

Project description:Rift Valley fever virus Raw sequence reads

| PRJNA518058 | ENA

Correlative Gene Expression to Protective Seroconversion in Rift Valley Fever Vaccinates.

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