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Potency of a thermostabilised chimpanzee adenovirus Rift Valley Fever vaccine in cattle.

ABSTRACT: Development of safe and efficacious vaccines whose potency is unaffected by long-term storage at ambient temperature would obviate major vaccine deployment hurdles and limit wastage associated with breaks in the vaccine cold chain. Here, we evaluated the immunogenicity of a novel chimpanzee adenovirus vectored Rift Valley Fever vaccine (ChAdOx1-GnGc) in cattle, following its thermostabilisation by slow desiccation on glass fiber membranes in the non-reducing sugars trehalose and sucrose. Thermostabilised ChAdOx1-GnGc vaccine stored for 6 months at 25, 37 or 45 ° C elicited comparable Rift Valley Fever virus neutralising antibody titres to those elicited by the 'cold chain' vaccine (stored at -80 ° C throughout) at the same dose, and these were within the range associated with protection against Rift Valley Fever in cattle. The results support the use of sugar-membrane thermostabilised vaccines in target livestock species.

SUBMITTER: Dulal P

PROVIDER: S-EPMC4851241 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Potency of a thermostabilised chimpanzee adenovirus Rift Valley Fever vaccine in cattle.

Dulal Pawan P Wright Daniel D Ashfield Rebecca R Hill Adrian V S AV Charleston Bryan B Warimwe George M GM

Vaccine 20160325 20

Development of safe and efficacious vaccines whose potency is unaffected by long-term storage at ambient temperature would obviate major vaccine deployment hurdles and limit wastage associated with breaks in the vaccine cold chain. Here, we evaluated the immunogenicity of a novel chimpanzee adenovirus vectored Rift Valley Fever vaccine (ChAdOx1-GnGc) in cattle, following its thermostabilisation by slow desiccation on glass fiber membranes in the non-reducing sugars trehalose and sucrose. Thermos ...[more]

PMID: 27020712

Similar Datasets

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.

| S-EPMC4742904 | biostudies-literature

Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

Project description:BackgroundRift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens.MethodsHere, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice.ResultsA single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response.ConclusionsTogether the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

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Current Status of Rift Valley Fever Vaccine Development.

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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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.

| S-EPMC4906348 | biostudies-other

An Overview of Rift Valley Fever Vaccine Development Strategies.

Project description:Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that causes high fetal and neonatal mortality in ruminants and a mild to fatal hemorrhagic fever in humans. There are no licensed RVF vaccines for human use while for livestock, commercially available vaccines are all either live attenuated or inactivated and have undesirable characteristics. The live attenuated RVF vaccines are associated with teratogenicity and residual virulence in ruminants while the inactivated ones require multiple immunisations to induce and maintain protective immunity. Additionally, nearly all licensed RVF vaccines lack the differentiating infected from vaccinated animals (DIVA) property making them inappropriate for use in RVF nonendemic countries. To address these limitations, novel DIVA-compatible RVF vaccines with better safety and efficacy than the licensed ones are being developed, aided fundamentally by a better understanding of the molecular biology of the RVF virus and advancements in recombinant DNA technology. For some of these candidate RVF vaccines, sterilizing immunity has been demonstrated in the discovery/feasibility phase with minimal adverse effects. This review highlights the progress made to date in RVF vaccine research and development and discusses the outstanding research gaps.

| S-EPMC9697312 | biostudies-literature

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

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| S-EPMC7248559 | biostudies-literature

Single-dose of a replication-competent adenovirus-vectored vaccine provides sterilizing protection against Rift Valley fever virus challenge.

Project description:Rift Valley fever virus (RVFV) is one of the most important virulent pathogens causing severe disease in animals and humans. However, there is currently no approved vaccine to prevent RVFV infection in humans. The use of human adenovirus serotype 4 (Ad4) as a vector for an RVFV vaccine has not been reported. Here, we report the generation of a replication-competent recombinant Ad4 vector expressing codon-optimized forms of the RVFV glycoproteins Gn and Gc (named Ad4-GnGc). Intramuscular immunization with Ad4-GnGc elicited robust neutralizing antibodies against RVFV and cellular immune responses in mice. A single low-dose vaccination with Ad4-GnGc completely protected interferon-α/β receptor-deficient A129 mice from lethal RVFV infection. More importantly, Ad4-GnGc efficacy was not affected by pre-existing immunity to adenovirus serotype 5, which currently exists widely in populations. These results suggest that Ad4-GnGc is a promising vaccine candidate against RVFV.

| S-EPMC9691644 | biostudies-literature

Rift Valley fever virus

Project description:Rift Valley fever virus Raw sequence reads

| PRJNA518058 | ENA

Rift Valley fever virus

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

| PRJNA517473 | ENA

A protective bivalent vaccine against Rift Valley fever and bluetongue.

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