Prevention of Vaccinia Lesions in Rhesus Monkeys by Human Leucocyte and Fibroblast Interferon

Weimar, Willem; Stitz, Lothar; Billiau, Alfons; Cantell, K; Schellekens, Huub

doi:10.1099/0022-1317-48-1-25

Cited by 22 publications

(9 citation statements)

References 13 publications

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“…Previous reports have shown that exogenously introduced type I IFN protects non-human primates from lesion development after vaccinia virus challenge [44], and IFN-β expressed by a recombinant vaccinia virus is 100% effective at preventing mortality in mice [43,44]. Here, we showed that IFN-β is capable of significantly reducing MPXV infection.…”

Section: Discussionsupporting

confidence: 58%

“…Type I IFN has been shown to protect mice and non-human primates from morbidity and mortality after challenge with the closely related vaccinia virus [43,44]. Additionally, studies have shown that as little as a 1-2 log reduction in MPXV significantly reduces morbidity and mortality in non-human primates [55].…”

Section: Discussionmentioning

confidence: 99%

“…Although IFN-β has been shown to substantially diminish vaccinia virus pathogenesis in vivo [43,44], the susceptibility of MPXV to IFN-β is uncertain. In this study, we found that MPXV production and release were significantly reduced in the presence of IFN-β.…”

Section: Introductionmentioning

confidence: 99%

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In vitro inhibition of monkeypox virus production and spread by Interferon-β

Johnston

Lin

Connor

et al. 2012

Virol J

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BackgroundThe Orthopoxvirus genus contains numerous virus species that are capable of causing disease in humans, including variola virus (the etiological agent of smallpox), monkeypox virus, cowpox virus, and vaccinia virus (the prototypical member of the genus). Monkeypox is a zoonotic disease that is endemic in the Democratic Republic of the Congo and is characterized by systemic lesion development and prominent lymphadenopathy. Like variola virus, monkeypox virus is a high priority pathogen for therapeutic development due to its potential to cause serious disease with significant health impacts after zoonotic, accidental, or deliberate introduction into a naïve population.ResultsThe purpose of this study was to investigate the prophylactic and therapeutic potential of interferon-β (IFN-β) for use against monkeypox virus. We found that treatment with human IFN-β results in a significant decrease in monkeypox virus production and spread in vitro. IFN-β substantially inhibited monkeypox virus when introduced 6-8 h post infection, revealing its potential for use as a therapeutic. IFN-β induced the expression of the antiviral protein MxA in infected cells, and constitutive expression of MxA was shown to inhibit monkeypox virus infection.ConclusionsOur results demonstrate the successful inhibition of monkeypox virus using human IFN-β and suggest that IFN-β could potentially serve as a novel safe therapeutic for human monkeypox disease.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

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In vitro inhibition of monkeypox virus production and spread by Interferon-β

Johnston

Lin

Connor

et al. 2012

Virol J

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“…Single daily doses of rIFNa or rIFNc rescued mice from lethality when administered 1-2 days after virus challenge and reduced lung virus titers. Both vaccinia keratitis and vaccinia-induced skin lesions were treated with rIFN (topically and injected respectively) in monkey models with success [10,11]. Vaccinia and other poxviruses have evolved comprehensive mechanisms to antagonize the interferon system [12], that include blocking IFN gene induction, disrupting extracellular and intracellular signaling and slowing IFN induced gene (PKR and 2959 OAS) activation.…”

Section: Introductionmentioning

confidence: 99%

Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201)

et al. 2011

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An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal vaccinia virus (WR strain) respiratory infections in mice. mDEF201 was administered as a single intranasal treatment either prophylactically or therapeutically at doses of 106 to 108 plaque forming units/mouse. When the prophylactic treatment was given at 56 days prior to infection, it protected 90% of animals from death (100% protection for treatments given between 1–49 days pre-infection), with minimal weight loss occurring during infection. Surviving animals re-challenged with virus 22 days after the primary infection were protected from death, indicating that mDEF201 did not compromise the immune response against the initial infection. Post-exposure therapy was given between 6–24 h after vaccinia virus exposure and protection was afforded by a 108 dose of mDEF201 given at 24 h, whereas a 107 dose was effective up to 12 h. Comparisons were made of the ability of mDEF201, given either 28 or 1 day prior to infection, to inhibit tissue virus titers and lung infection parameters. Lung, liver, and spleen virus titers were inhibited to nearly the same extent by either treatment, as were lung weights and lung hemorrhage scores (indicators of pneumonitis). Lung virus titers were significantly (>100-fold) lower than in the placebo group, and the other infection parameters in mDEF201 treated mice were nearly at baseline. In contrast, viral titers and lung infection parameters were high in the placebo group on day 5 of the infection. These results demonstrate the long-acting prophylactic and treatment capacity of mDEF201 to combat vaccinia virus infections.

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“…In three field trials, methisazone (Marboran) was used as an effective prophylactic drug (48). Moreover, human leukocyte and fibroblast interferons have been effectively used for the prevention of vaccinia lesions in monkeys (106). Adenine arabinoside and cytosine arabinoside proved ineffective in the treatment of variola major (62,82).…”

Section: The Diseasementioning

confidence: 99%