EFFECTIVE PROPHYLAXIS OF INFLUENZA-A VIRUS PNEUMONIA IN MICE BY TOPICAL PASSIVE IMMUNOTHERAPY WITH POLYVALENT HUMAN-IMMUNOGLOBULINS OR F(AB')(2) FRAGMENTS

The effectiveness of polyvalent plasma-derived human immunoglobulins ( IVIG) in passive immunotherapy of influenza virus pneumonia was assess ed, using the Strain Scotland (A/Scotland/74 (H3N2)) adapted to BALB/c mice by repeated lung passages. Haemagglutinin antibodies in two batc hes of IVIG at 10 mg/ml had a titre of 1/16. Intravenous injection of 1000-5000 mu g of IVIG, 3 h after infection, gave 60-70% protection, w hereas intranasal injection of 25-50 mu g protected 90% of mice infect ed with a lethal dose of influenza virus. F(ab')(2) fragments were at least as protective as intact IVIG, suggesting that complement or Fc g amma receptor-bearing cells were not required. Topical passive immunot herapy with IVIG or F(ab')(2) gave protection up to 8 h after infectio n, but not at 24 h, suggesting that anti-influenza A antibodies in IVI G, delivered locally, are only effective at early stages of the infect ious 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 administra tion 24 h before challenge.