Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge

The efficacy of cidofovir for treatment of cowpox virus infection in BALB/c mice was investigated in an effort to evaluate new therapies for virulent orthopoxvirus infections of the respiratory tract in a small animal model. Exposure to 2-5 x 10(6) pfu of cowpox virus by aerosol or intranasally (inl ) was lethal in 3- to 7-week-old animals, One inoculation of 100 mg/kg cido fovir on day 0, 2, or 4, with respect to aerosol infection, resulted in 90% -100% survival. Treatment on day 0 reduced peak pulmonary virus titers 10- to 100-fold, reduced the severity of viral pneumonitis, and prevented pulmo nary hemorrhage. The same dose on day -6 to 2 protected 80%-100% of inl inf ected mice, whereas 1 inoculation on day -16 to -8 or day 3 to 6 was partia lly protective. Cidofovir delayed but did not prevent the death of inl infe cted mice with severe combined immunodeficiency, Treatment at the time of t ail scarification with vaccinia virus did not block vaccination efficacy.