METHODS AND COMPOSITIONS FOR PRODUCING AN ADENOVIRUS VECTOR FOR USE WITH MULTIPLE VACCINATIONS
Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided.
1 .- 36 . (canceled)
37 . A composition comprising a replication defective adenovirus vector comprising 1) a deletion in the E2b region and 2) a nucleic acid sequence encoding a protein having a therapeutic effect.
38 . The composition of claim 37 , wherein the replication defective adenovirus vector further comprises a deletion in the E1 region.
39 . The composition of claim 37 , wherein the nucleic acid sequence encoding the antigen is located in the E1 region.
40 . The composition of claim 37 , wherein the replication defective adenovirus vector further comprises a deletion in the E3 region.
41 . The composition of claim 37 , wherein the nucleic acid sequence encoding the antigen is located in the E3 region.
42 . The composition of claim 37 , wherein the replication defective adenovirus vector is derived from Adenovirus serotype 5.
43 . The composition of claim 37 , wherein the composition comprises the replication defective adenovirus vector at a concentration of at least 10 10 virus particles/ml.
44 . The composition of claim 37 , wherein the replication defective adenovirus vector is not helper-adenovirus dependent.
45 . The composition of claim 37 , wherein the protein is selected from the group consisting of an antibody, an anti-bacterial protein, an anti-viral protein, an anti-tumor protein, and an immune modulator protein.
46 . The composition of claim 45 , wherein the protein is an immune modulatory protein.
47 . The composition of claim 37 , further comprising an adjuvant.
48 . The composition of claim 47 , wherein the adjuvant is granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), IL-7, IL-12, IL-4, IL-5, IL-6, IL-10, IL-12, or a combination thereof.
49 . The composition of claim 37 , wherein the composition is formulated for intramuscular, subcutaneous, or intradermal administration.
50 . The composition of claim 37 , wherein the composition comprises the replication defective adenovirus vector at a concentration of at least 10 9 virus particles/ml.
51 . The composition of claim 37 , wherein the antigen has been modified to increase immunogenicity.
52 . The composition of claim 37 , further comprising a second replication defective adenovirus vector comprising a deletion in the E2b region and a nucleic acid sequence encoding an adjuvant.
53 . A cell comprising the composition of claim 37 .
54 . The cell of claim 53 , wherein the cell constitutively expresses DNA polymerase and preterminal protein.
55 . The cell of claim 54 , wherein the cell is an antigen presenting cell.