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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.

Project description:Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A 'One Health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs.

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Project description:Rift Valley Fever (RVF) is a mosquito-borne zoonotic disease that presents a substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Phenuiviridae within the order Bunyavirales. The wide distribution of competent vectors in non-endemic areas coupled with global climate change poses a significant threat of the transboundary spread of RVFV. In the last decade, an improved understanding of the molecular biology of RVFV has facilitated significant progress in the development of novel vaccines, including DIVA (differentiating infected from vaccinated animals) vaccines. Despite these advances, there is no fully licensed vaccine for veterinary or human use available in non-endemic countries, whereas in endemic countries, there is no clear policy or practice of routine/strategic livestock vaccinations as a preventive or mitigating strategy against potential RVF disease outbreaks. The purpose of this review was to provide an update on the status of RVF vaccine development and provide perspectives on the best strategies for disease control. Herein, we argue that the routine or strategic vaccination of livestock could be the best control approach for preventing the outbreak and spread of future disease.

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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.

2016-09-16 | GSE71417 | GEO

Protection of Cattle Elicited Using a Bivalent Lumpy Skin Disease Virus-Vectored Recombinant Rift Valley Fever Vaccine.

Project description:Lumpy skin disease and Rift Valley fever are two high-priority livestock diseases which have the potential to spread into previously free regions through animal movement and/or vectors, as well as intentional release by bioterrorists. Since the distribution range of both diseases is similar in Africa, it makes sense to use a bivalent vaccine to control them. This may lead to the more consistent and sustainable use of vaccination against Rift Valley fever through a more cost-effective vaccine. In this study, a recombinant lumpy skin disease virus was constructed in which the thymidine kinase gene was used as the insertion site for the Gn and Gc protective glycoprotein genes of Rift Valley fever virus using homologous recombination. Selection markers, the enhanced green fluorescent protein and Escherichia coli guanidine phosphoribosyl transferase (gpt), were used for selection of recombinant virus and in a manner enabling a second recombination event to occur upon removal of the gpt selection-pressure allowing the removal of both marker genes in the final product. This recombinant virus, LSD-RVF.mf, was selected to homogeneity, characterized and evaluated in cattle as a vaccine to show protection against both lumpy skin disease and Rift Valley fever in cattle. The results demonstrate that the LSD-RVF.mf is safe, immunogenic and can protect cattle against both diseases.

| S-EPMC7248559 | biostudies-literature

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.

2022-04-27 | GSE200881 | GEO

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.

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 RVF vaccine, authentic recombinant MP-12 (arMP-12). From previous work, protective immunity in sheep and cattle vaccinates normally occurs from 7 to 21 days after inoculation with arMP-12. While the serology and protective response induced by arMP-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 of vaccinated calves over a time course of 21 days before and after vaccination with arMP-12. The time course RNAs were sequenced by RNASeq and bioinformatically analyzed. Our results revealed time-dependent activation or repression of numerous gene ontologies and pathways related to the vaccine induced immune response and its regulation. Additional bioinformatic analyses identified a correlative relationship between specific host immune response genes and protective immunity prior to the detection of protective serum neutralizing antibody responses. These results contribute an important proof of concept for identifying molecular and genetic components underlying the immune response to RVF vaccination and protection prior to serologic detection.

| S-EPMC4718665 | biostudies-literature

Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats.

Project description:Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus that was first discovered in Kenya in 1930 and has since spread to become endemic in much of Africa and the Arabian Peninsula. Rift Valley fever (RVF) causes recurrent outbreaks of febrile illness associated with high levels of mortality and poor outcomes during pregnancy-including foetal malformations, spontaneous abortion and stillbirths-in livestock, and associated with miscarriage in humans. No vaccines are available for human use and those licensed for veterinary use have potential drawbacks, including residual virulence that may contraindicate their use in pregnancy. To address this gap, we previously developed a simian adenovirus vectored vaccine, ChAdOx1 RVF, that encodes RVFV envelope glycoproteins. ChAdOx1 RVF is fully protective against RVF in non-pregnant livestock and is also under development for human use. Here, we now demonstrate that when administered to pregnant sheep and goats, ChAdOx1 RVF is safe, elicits high titre RVFV neutralizing antibody, and provides protection against viraemia and foetal loss, although this protection is not as robust for the goats. In addition, we provide a description of RVFV challenge in pregnant goats and contrast this to the pathology observed in pregnant sheep. Together, our data further support the ongoing development of ChAdOx1 RVF vaccine for use in livestock and humans.

| S-EPMC6802222 | biostudies-literature

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