Rapid and prolonged immunogenic-therapeutic

Abstract

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

1 - 19 . (canceled) 
     
     
         20 . A pharmaceutical formulation suitable for a single dose intranasal administration to a mammalian subject, comprising:
 an effective amount of at least 10 7  infectious units (ifu) of E1 and/or E3 defective adenovirus vector that contains and expresses influenza virus hemagglutinin antigen codon optimized for the mammalian subject, wherein the effective amount induces a protective immune response within 24 hours of administration; and,   a pharmaceutically acceptable diluent or carrier.   
     
     
         21 . The formulation of  claim 20 , wherein the influenza virus is swine influenza, seasonal influenza, avian influenza, influenza A type, H1N1 influenza or H5N1 influenza. 
     
     
         22 . The formulation of  claim 20 , wherein the mammalian subject is a human. 
     
     
         23 . The formulation of  claim 20 , wherein the adenovirus is a human adenovirus. 
     
     
         24 . The formulation of  claim 20 , wherein the adenovirus is a bovine adenovirus, a canine adenovirus, a non-human primate adenovirus, a chicken adenovirus, or a porcine or swine adenovirus. 
     
     
         25 . The formulation of  claim 20 , wherein the protective response lasts at least 47 days. 
     
     
         26 . The formulation of  claim 20 , wherein the effective amount is at least 10 7  infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus. 
     
     
         27 . The formulation of  claim 20 , wherein the effective amount is at least 10 8  infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus. 
     
     
         28 . The formulation of  claim 20 , wherein the effective amount is at least 10 9  infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus. 
     
     
         29 . The formulation of  claim 20 , wherein the composition is in a form of a liquid, emulsion, solid, aerosol or gas. 
     
     
         30 . A pharmaceutical formulation suitable for a two-dose intranasal administration to a mammalian subject, comprising:
 an effective amount of at least 10 7  infectious units (ifu) of E1 and/or E3 defective adenovirus vector that contains and expresses a  Bacillus anthracis  antigen codon optimized for the mammalian subject, wherein the two doses induces a protective response that provides protection against challenge with intranasal inhalation of  Bacillus anthracis  spores; and,   a pharmaceutically acceptable diluent or carrier.   
     
     
         31 . The formulation of  claim 30 , wherein the  Bacillus anthracis  antigen is protective antigen. 
     
     
         32 . The formulation of  claim 30 , wherein the  Bacillus anthracis  antigen is lethal factor. 
     
     
         33 . The formulation of  claim 30 , wherein the mammalian subject is a human. 
     
     
         34 . The formulation of  claim 30 , wherein the adenovirus is a human adenovirus. 
     
     
         35 . The formulation of  claim 30 , wherein the adenovirus is a bovine adenovirus, a canine adenovirus, a non-human primate adenovirus, a chicken adenovirus, or a porcine or swine adenovirus. 
     
     
         36 . The formulation of  claim 30 , wherein the effective amount is at least 10 7  infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus. 
     
     
         37 . The formulation of  claim 30 , wherein the effective amount is at least 10 8  infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus. 
     
     
         38 . The formulation of  claim 30 , wherein the effective amount is at least 10 9  infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus. 
     
     
         39 . The formulation of  claim 30 , wherein the composition is in a form of a liquid, emulsion, solid, aerosol or gas.