Rapid and prolonged immunologic-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. A method of inducing a protective immune response against inhalation anthrax in a mammalian subject in need thereof comprising:
administering intranasally, a single dose of an effective amount of at least 10 7 infectious units (ifu) of E1 and/or E3 deleted adenovirus that contains and expresses a Bacillus anthracis antigen codon optimized for the mammalian subject,
wherein induction of the protective response provides protection against challenge with intranasal inhalation of Bacillus anthracis spores and thereby non-invasively inducing a protective immune response against inhalation anthrax in the mammal.
2. The method of claim 1 , wherein the Bacillus anthracis antigen is protective antigen.
3. The method of claim 1 , wherein the Bacillus anthracis antigen is lethal factor.
4. The method of claim 1 , wherein the effective amount is at least 10 8 infectious units (ifu) of E1 and/or E3 deleted adenovirus.
5. The method of claim 1 , wherein the effective amount is at least 10 8 infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus.
6. The method of claim 1 , wherein the effective amount is at least 10 9 infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus.
7. The method of claim 1 wherein the subject in need thereof is an adult.
8. The method of claim 1 wherein the subject in need thereof is a child.
9. The method of claim 1 wherein the subject in need thereof is an immunocompromised patient.
10. The method of claim 1 wherein the adenovirus is a human adenovirus.
11. The method of claim 1 wherein the adenovirus is a bovine adenovirus, a canine adenovirus, a non-human primate adenovirus, a chicken adenovirus, or a porcine or swine adenovirus.
12. A method of inducing a protective immune response against inhalation anthrax in a mammalian subject in need thereof comprising:
administering intranasally, a single dose of an effective amount of at least 10 7 infectious units (ifu) of E1 and/or E3 deleted adenovirus that contains and expresses a Bacillus anthracis antigen,
wherein induction of the protective response provides protection against challenge with intranasal inhalation of Bacillus anthracis spores and thereby non-invasively inducing a protective immune response against inhalation anthrax in the mammal.
13. The method of claim 12 , wherein the Bacillus anthracis antigen is protective antigen.
14. The method of claim 12 , wherein the Bacillus anthracis antigen is lethal factor.
15. The method of claim 12 , wherein the effective amount is at least 10 8 infectious units (ifu) of E1 and/or E3 deleted adenovirus.
16. The method of claim 12 , wherein the effective amount is at least 10 8 infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus.
17. The method of claim 12 , wherein the effective amount is at least 10 9 infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus.
18. A method of inducing a protective immune response against inhalation anthrax in a mammalian subject in need thereof comprising:
administering intranasally, a single dose of an effective amount of at least 10 7 infectious units (ifu) of E1 and/or E3 deleted adenovirus that contains and expresses a Bacillus anthracis protective antigen,
wherein induction of the protective response provides protection against challenge with intranasal inhalation of Bacillus anthracis spores and thereby non-invasively inducing a protective immune response against inhalation anthrax in the mammal.