Efficacy of Cidofovir in a Murine Model of Disseminated Progressive Vaccinia

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Abstract
An animal model that mimics progressive disseminated vaccinia was elaborated. To this end nude (athymic) mice were inoculated intracutaneously with vaccinia virus in the lumbosacral area. Viral replication (DNA) in the skin was detected as early as day 2 postinfection (p.i.). Mice developed typical vaccinia lesions at the site of inoculation by day 4 to 6 p.i. By about 2 weeks p.i., the infection had spread all over the body, a situation reminiscent of disseminated vaccinia in humans. The infection resulted in viremia and spread of the virus to visceral organs, as well as to the brain. Topical treatment with cidofovir, initiated at the day of infection or at day 1 p.i., completely protected against virus-induced cutaneous lesions and against associated mortality. When treatment was initiated at a later time (day 2 to 5 p.i.), a partial but marked protective effect was noted, which can be explained by the fact that by that time, the virus had spread from the skin to the visceral organs. Next, infected animals were left untreated until the time (∼2 weeks p.i.) at which disseminated vaccinia had developed. When systemic treatment with cidofovir was initiated at that time, it caused lesions to heal and regress. In most of these animals, lesions had completely (or almost completely) disappeared by day 10 to 15 after the start of therapy. The observation that cidofovir is able to cause healing of disseminated vaccinia lesions in animals should have implications for the therapy of complications of vaccination against smallpox.