Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge

Gowen, Brian B.; Bailey, Kevin W.; Scharton, Dionna; Vest, Zachery; Westover, Jonna B.; Skirpstunas, Ramona T.; Ikegami, Tetsuro

doi:10.1016/j.antiviral.2013.03.009

Cited by 19 publications

(25 citation statements)

References 28 publications

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“…Consistent with earlier studies reporting a high degree of susceptibility, hamsters succumbed to a 10 PFU challenge with the ZH501 strain of RVFV within 2 to 3 days. By comparison, C57BL/6J mice challenged with 100× more PFU of the same virus stock succumbed in 3 to 6 days [ 36 ], underscoring the heightened sensitivity of hamsters to acute RVFV-induced disease.…”

Section: Discussionmentioning

confidence: 99%

Rift Valley Fever Virus Infection in Golden Syrian Hamsters

et al. 2015

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Rift Valley fever virus (RVFV) is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies.

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Section: Discussionmentioning

confidence: 99%

Rift Valley Fever Virus Infection in Golden Syrian Hamsters

et al. 2015

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“…Virus titers were assayed using an infectious cell culture assay as previously described (Gowen et al, 2013). Briefly, a specific volume of tissue homogenate or serum was serially diluted and added to triplicate wells of Vero 76 cell monolayers in 96-well microtiter plates.…”

Section: Methodsmentioning

confidence: 99%

Favipiravir (T-705) protects against peracute Rift Valley fever virus infection and reduces delayed-onset neurologic disease observed with ribavirin treatment

et al. 2014

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Rift Valley Fever is a zoonotic, arthropod-borne disease that affects livestock and humans. The etiologic agent, Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) is primarily transmitted through mosquito bites, but can also be transmitted by exposure to infectious aerosols. There are presently no licensed vaccines or therapeutics to prevent or treat severe RVFV infection in humans. We have previously reported on the activity of favipiravir (T-705) against the MP-12 vaccine strain of RVFV and other bunyaviruses in cell culture. In addition, efficacy has also been documented in mouse and hamster models of infection with the related Punta Toro virus. Here, we challenged hamsters with the highly pathogenic ZH501 strain of RVFV to evaluate the activity of favipiravir against lethal infection. Subcutaneous RVFV challenge resulted in substantial serum and tissue viral loads and caused severe disease and mortality within 2–3 days after infection. Oral favipiravir (200 mg/kg/day) prevented mortality in 60% or greater in hamsters challenged with RVFV when administered within 1 or 6 h post-exposure and reduced RVFV titers in serum and tissues relative to the time of treatment initiation. In contrast, although ribavirin (75 mg/kg/day) was effective at protecting animals from the peracute RVFV disease, most ultimately succumbed from a delayed-onset neurologic disease associated with high RVFV burden in the brain observed in moribund animals. When combined, T-705 and ribavirin treatment started 24 h post-infection significantly improved survival outcome and reduced serum and tissue virus titers compared to monotherapy. Our findings demonstrate significant post-RVFV exposure efficacy with favipiravir against both peracute disease and delayed-onset neuroinvasion, and suggest added benefit when combined with ribavirin.

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“…For those who become infected and develop hemorrhagic fever or encephalitis, current medicine may not support prophylaxis. Post-exposure vaccination with rMP12-ΔNSs16/198 showed reduction of pathogenic RVFV replication in liver or spleen, and resulted in improved survival rate in highly susceptible mice and hamsters [96,97]. Future studies should also identify antivirals or other biologicals which can rapidly reduce viral replication and support recovery from late stages of infection.…”

Section: Five-year Viewmentioning

confidence: 99%

Rift Valley fever vaccines: an overview of the safety and efficacy of the live-attenuated MP-12 vaccine candidate

Ikegami

2017

Expert Review of Vaccines

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Introduction Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Arabian Peninsula. High rates of abortion among infected ruminants and hemorrhagic fever in infected humans are major public health concerns. Commercially available veterinary RVF vaccines are important for preventing the spread of the Rift Valley fever virus (RVFV) in endemic countries; however, RVFV outbreaks continue to occur frequently in endemic countries in the 21st century. In the U.S., the live-attenuated MP-12 vaccine has been developed for both animal and human vaccination. This vaccine strain is well attenuated, and a single dose induces neutralizing antibodies in both ruminants and humans. Areas covered This review describes scientific evidences of MP-12 vaccine efficacy and safety, as well as MP-12 variants recently developed by reverse genetics, in comparison with other RVF vaccines. Expert commentary The containment of active RVF outbreaks and long-term protection from RVF exposure to infected mosquitoes are important goals for RVF vaccination. MP-12 vaccine will allow immediate vaccination of susceptible animals in case of an unexpected RVF outbreak in the U.S., whereas MP-12 vaccine may be also useful for the RVF control in endemic regions.

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Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge

Cited by 19 publications

References 28 publications

Rift Valley Fever Virus Infection in Golden Syrian Hamsters

Rift Valley Fever Virus Infection in Golden Syrian Hamsters

Favipiravir (T-705) protects against peracute Rift Valley fever virus infection and reduces delayed-onset neurologic disease observed with ribavirin treatment

Rift Valley fever vaccines: an overview of the safety and efficacy of the live-attenuated MP-12 vaccine candidate

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