Composition and methods based on neutralizing antibodies delivered intranasally for enhanced therapeutic efficacy

Abstract

The present invention provides methods for treatment or prophylaxis of viruses, particularly influenza virus, by administration of agents, particularly neutralizing antibodies or active fragments thereof, directly to the respiratory tract, including by intranasal or inhalation administration. The invention provides compositions suitable for intranasal or inhalation treatment and administration. The invention includes methods for treatment or prophylaxis combining intranasal or inhalation administration with intraperitoneal or intravenous administration of antibodies.

1 . A composition formulated for intranasal or inhalation administration and effective for treatment or prophylaxis of influenza viral infection in a mammal comprising an effective amount of two or more influenza virus neutralizing monoclonal IgG antibodies capable of neutralizing influenza A virus of at least two HA subtypes in a single unit dose of 1 mg/kg or less. 
     
     
         2 . The composition of  claim 1  comprising the influenza virus neutralizing monoclonal antibodies in a single unit dose of less than 0.5 mg/kg. 
     
     
         3 . The composition of  claim 1  comprising the influenza virus neutralizing monoclonal antibodies in a single unit dose of less than 0.1 mg/kg. 
     
     
         4 . The composition of  claim 1  comprising the influenza virus neutralizing monoclonal antibodies in a single unit dose of less than 0.05 mg/kg. 
     
     
         5 . The composition of  claim 1  wherein one or more of the influenza virus neutralizing monoclonal antibodies is an antibody fragment capable of influenza neutralization and selected from Fab, Fab′, and F(ab′)2. 
     
     
         6 . The composition of  claim 1  further comprising a pharmaceutically acceptable excipient, carrier or diluent, an additive for nasal or pulmonary delivery, or an immunological mediator or stimulator of the immune response. 
     
     
         7 . The composition of  claim 1  comprising a combination of influenza neutralizing antibodies comprising an antibody capable of neutralizing influenza A H1 virus, an antibody capable of neutralizing influenza A H3 virus, and an antibody capable of neutralizing influenza B virus.