Effective prophylaxis of influenza A virus pneumonia in mice by topical passive immunotherapy with polyvalent human immunoglobulins or F(ab')2 fragments

Abstract

The effectiveness of polyvalent plasma-derived human immunoglobulins (IVIG) in passive immunotherapy of influenza virus pneumonia was assessed, using the Strain Scotland (A/Scotland/74 (H3N2)) adapted to BALB/c mice by repeated lung passages. Haemagglutinin antibodies in two batches of IVIG at 10mg/ml had a titre of 1/16. Intravenous injection of 1000-5000 μg of IVIG, 3h after infection, gave 60-70% protection, whereas intranasal injection of 25-50 μg protected 90% of mice infected with a lethal dose of influenza virus. F(ab')2 fragments were at least as protective as intact IVIG, suggesting that complement or Fcγ receptor-bearing cells were not required. Topical passive immunotherapy with IVIG or F(ab')2 gave protection up to 8 h after infection, but not at 24 h, suggesting that anti-influenza A antibodies in IVIG, delivered locally, are only effective at early stages of the infectious process. The potential value of topical administration of IVIG or F(ab')2 fragments for influenza A pneumonia prophylaxis was further demonstrated by the protective effects of their intranasal administration 24 h before challenge.