Prevention of lethal respiratory vaccinia infections in mice with interferon-α and interferon-γ

The antiviral efficacy of interferons (IFNs) was evaluated using a vaccinia intranasal infection model in mice in this study. We provide evidence that intranasal administration of IFN-α and IFN-γ (days −1 to +3) resulted in 100 and 90% survival against a lethal respiratory vaccinia infection (8 LD 50) in mice, respectively; whereas no animals in the placebo group survived through the study period (21 days). The IFN treatment consisted of a single daily dose of 5×10 3 U per mouse for 5 consecutive days. The efficacy of IFN-γ was evident even when the IFN-γ treatments started 1–2 days after infection and when a lower dose (2×10 3 U per mouse) was used. The treatment of IFN-α and IFN-γ reduced the virus titers in the lungs of infected mice by 1000–10 000-fold, when the administration started 1 day after infection. Our data suggest that IFN-α and IFN-γ are effective in protecting vaccinia-infected mice from viral replication in lungs and mortality, and may be beneficial in other human orthopoxvirus infections.