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 for an immune response against of influenza infection in a mammalian subject in need thereof comprising:
administering intranasally, during a period within 1-2 days before exposure to an influenza virus, an effective amount of at least 10 7 infectious units (ifu) of E1 and/or E3 deleted adenovirus that contains and expresses an influenza virus antigen codon optimized for the mammalian subject,
wherein a protective response against the influenza virus begins within twenty four hours of administration and lasts at least 21 days providing treatment to the mammalian subject at risk of the influenza infection.
2. The method of claim 1 , wherein the influenza virus is swine influenza, seasonal influenza, avian influenza, H1N1 influenza, or H5N1 influenza.
3. The method of claim 2 , wherein the influenza virus antigen is influenza hemagglutinin, influenza nuclear protein or influenza M2.
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 further comprising at least two steps of administering.
11. The method of claim 10 wherein the administering is 40 days apart, 41 days apart, 42 days apart, 43 days apart, 44 days apart, 45 days apart, 46 days apart, 47 days apart, 48 days apart, 49 days apart or 50 days apart.
12. The method of claim 1 wherein the adenovirus is a human adenovirus.
13. 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.
14. A method for an immune response against of an influenza infection in a mammalian subject in need thereof comprising:
administering intranasally, at least once during a period within 1-2 days before exposure to influenza virus, an effective amount of at least 10 7 infectious units (ifu) of E1 and/or E3 deleted adenovirus that contains and expresses an influenza virus antigen,
wherein a protective response begins within twenty four hours of administration and lasts at least 21 days providing treatment to the mammalian subject at risk of the influenza infection.