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 10 mg/ml had a titre of 1/16. Intravenous injection of 1000-5000 microg of IVIG, 3 h after infection, gave 60-70% protection, whereas intranasal injection of 25-50 microg 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 Fcgamma 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.

Effective Combination Therapy for Invasive Pneumococcal Pneumonia with Ampicillin and Intravenous Immunoglobulins in a Mouse Model

“…Topical immunotherapy is a promising approach for epithelial infections (27,29), particularly for pulmonary infections (22,23,24). In this study, intranasal administration of IVIG was effective against pneumonia induced by various lethal pneumococcal inocula of 10 to 1,000 times the LD 50 but did not significantly neutralize bacteremia, which is the major threat in pneumococcal infections (13,20), probably due to the short lifetime of IVIG in the lungs after intranasal administration.…”

Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

“…The intranasal route was examined because of a prior report demonstrating that IVIg is protective when delivered intranasally to mice prior to influenza challenge, albeit at a dose of IVIg 80–400 times the human dose/kg equivalent (Ramisse et al, 1998). A negative control group of animals was given diluent only intravenously 2 prior to challenge.…”

Virus-Neutralizing Activity Mediated by the Fab Fragment of a Hemagglutinin-Specific Antibody Is Sufficient for the Resolution of Influenza Virus Infection in SCID Mice

“…Divergent findings were made, however, with VN-positive Abs. The majority of studies (19-21, 37, 49, 52), including one dealing with influenza virus (38), concluded that Fc-dependent activities were not required for Ab-mediated protection in vivo. In other cases, however, Fc-dependent activities appeared to play a substantial role (2,23,25,27,41).…”

“…administration required 100 to 160 times more Ab than i.n. administration (36,38). However, these comparisons One day after i.p.…”