RAPID AND PROLONGED IMMUNOGENIC-THERAPEUTIC
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.