Aerosol inhalation of human IFN-α1b exhibits anti-RSV activity in mice and favorable pharmacokinetics/safety in cynomolgus monkeys

Introduction Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, while effective therapeutic options remain limited. This study investigated the antiviral efficacy, pharmacokinetics, and safety of aerosolized human interferon-α1b (IFN-α1b) as a potential treatment for RSV infection. Methods The antiviral activity of IFN-α1b against RSV was evaluated in vitro and in an RSV-infected mouse model. Pharmacokinetics, tissue distribution, and repeat-dose inhalation toxicity were assessed in cynomolgus monkeys. Results IFN-α1b inhibited RSV in vitro (EC₅₀ of 4.64 ng/mL). In mice, aerosolized IFN-α1b reduced lung viral titers in a dose-dependent manner. Notably, the reduction in viral load across all IFN-α1b dose groups was greater than that observed in the ribavirin-treated group under the conditions tested ( p < 0.001). In monkeys, inhalation resulted in high respiratory drug exposure with an absolute systemic bioavailability of 3.33%. Repeated dosing (18 μg/kg/day) was well tolerated, with only minimal to mild (Grade 1 to 2) focal lung inflammation that was fully reversible. Conclusion Aerosolized IFN-α1b demonstrates antiviral activity and favorable lung-targeted pharmacokinetics in preclinical models, supporting further investigation in clinical settings. It was associated with greater reduction in lung viral titers compared with ribavirin in this model while maintaining a favorable safety profile.