Efficacy of a Rift Valley fever virus vaccine against an aerosol infection in rats

Anderson, G. W.; Lee, J.O.; Anderson, Arthur O.; Powell, Nathaniel; Mangiafico, Joseph A.; Meadors, Gilcin F.

doi:10.1016/0264-410x(91)90285-e

Cited by 34 publications

(33 citation statements)

References 14 publications

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“…The delayed death in these 6 rats was clinically associated with neurological signs such as tremor, head-tilt, and circling in their cage. Typically, Wistar-Furth rats succumb to RVFV infection prior to the development of neurological signs; however there is evidence that a small proportion of infected Wistar-Furth rats that survive beyond day 7 die of neurological disease [41], which is reminiscent of what is seen in ACI and Lewis rats infected with RVFV [31]. Unlike the infected untreated control rats, virus was found primarily within the brain of these 6 treated rats that died with neurological signs, with much lower levels in peripheral tissues and none detectable in the blood at necropsy (Fig.…”

Section: Resultsmentioning

confidence: 99%

Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever

et al. 2014

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BackgroundDevelopment of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705), which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV). RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route.Methodology/Principal FindingsWistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92%) survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease.Conclusions/SignificanceCurrently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug.

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Section: Resultsmentioning

confidence: 99%

Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever

et al. 2014

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“…Antibody-mediated virus clearance from infected neurons have also been described for alphaviruses and RVFV [228][229][230]. Nonetheless, antibody response appeared to be dispensable for clearance of VEEV from CNS [231].…”

Section: Viral Clearance From the Cnsmentioning

confidence: 86%

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

2016

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Arboviruses are arthropod-borne viruses that exhibit worldwide distribution, contributing to systemic and neurologic infections in a variety of geographical locations. Arboviruses are transmitted to vertebral hosts during blood feedings by mosquitoes, ticks, biting flies, mites, and nits. While the majority of arboviral infections do not lead to neuroinvasive forms of disease, they are among the most severe infectious risks to the health of the human central nervous system. The neurologic diseases caused by arboviruses include meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and myositis in which virus-and immune-mediated injury may lead to severe, persisting neurologic deficits or death. Here we will review the major families of emerging arboviruses that cause neurologic infections, their neuropathogenesis and host neuroimmunologic responses, and current strategies for treatment and prevention of neurologic infections they cause.

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“…Clearly, further investigation of SIN-based replicon vaccine against RVFV is warranted, with a need to establish the correlates of immunity to challenge more exactly, including determination of protective levels of neutralizing antibody, the potential role of nonneutralizing antibodies, plus the contributions of cellmediated and mucosal immune responses [39][40][41]. Ultimately, a vaccine requiring only a single immunization would be optimal, especially for livestock applications.…”

Section: Discussionmentioning

confidence: 99%

An alphavirus replicon-derived candidate vaccine against Rift Valley fever virus

Heise

Whitmore²,

Thompson

et al. 2009

Epidemiol. Infect.

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SUMMARY Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus (genus Phlebovirus)associated with severe disease in livestock and fatal encephalitis or haemorrhagic fever in a proportion of infected humans. Although live attenuated and inactivated vaccines have been used in livestock, and on a limited scale in humans, there is a need for improved anti-RVFV vaccines. Towards this goal, Sindbis virus replicon vectors expressing the RVFV Gn and Gc glycoproteins, as well as the non-structural nsM protein, were constructed and evaluated for their ability to induce protective immune responses against RVFV. These replicon vectors were shown to produce the RVFV glycoproteins to high levels in vitro and to induce systemic anti-RVFV antibody responses in immunized mice, as determined by RVFV-specific ELISA, fluorescent antibody tests, and demonstration of a neutralizing antibody response. Replicon vaccination also provided 100% protection against lethal RVFV challenge by either the intraperitoneal or intranasal route. Furthermore, preliminary results indicate that the replicon vectors elicit RVFV-specific neutralizing antibody responses in vaccinated sheep. These results suggest that alphavirus-based replicon vectors can induce protective immunity against RVFV, and that this approach merits further investigation into its potential utility as a RVFV vaccine.

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Efficacy of a Rift Valley fever virus vaccine against an aerosol infection in rats

Cited by 34 publications

References 14 publications

Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever

Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

An alphavirus replicon-derived candidate vaccine against Rift Valley fever virus

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