Evaluation of intravenous zanamivir against experimental influenza A (H5N1) virus infection in cynomolgus macaques
We investigated the prophylactic and therapeutic efficacy of an intravenous (IV) formulation of zanamivir in a macaque infection model for highly pathogenic influenza A (H5N1) virus. Antiviral efficacy was dose-dependent, with no reduction in viral load observed at 2 mg/kg, but a significant reduction observed at 10 mg/kg (p = 0.039) and at 20 mg/kg in the combined prophylactic and therapeutic groups (p = 0.049) with both prophylaxis (commencing 12 h before infection) and therapy (commencing 4 h after infection) showing similar reductions in viral load. Combined gross pathology and microscopic pneumonia scores in the treated animals relative to untreated controls were significantly reduced at 10 mg/kg (p = 0.02) and at 20 mg/kg in the prophylaxis group (p = 0.02), but were not significant in the treatment group (p = 0.145). In this new animal model for evaluation of influenza antivirals, despite variability observed between individual animals, IV zanamivir showed evidence of efficacy against highly pathogenic H5N1 virus.
|Keywords||Antiviral agents, Human influenza, Influenza A virus H5N1 subtype, Macaca fascicularis, Zanamivir|
|Persistent URL||dx.doi.org/10.1016/j.antiviral.2008.06.014, hdl.handle.net/1765/29289|
Stittelaar, K.J., Tisdale, M., van Amerongen, G., van Lavieren, R.F., Pistoor, F.H., Simon, J.H., & Osterhaus, A.D.M.E.. (2008). Evaluation of intravenous zanamivir against experimental influenza A (H5N1) virus infection in cynomolgus macaques. Antiviral Research, 80(2), 225–228. doi:10.1016/j.antiviral.2008.06.014