Adenoviral vectors comprising partial deletions of E3
This disclosure provides replication-incompetent adenoviral vectors useful in vaccine development and gene therapy. The disclosed vectors comprise a selective deletion of E3 and are particularly useful for preparation of vaccines development and for gene therapy using toxic transgene products that result in vector instability that occurs when the entire E3 domain is deleted.
1. A replication-incompetent adenovirus vector comprising:
a) open reading frame (ORF) ORF1 and ORF2 of E3 genomic region;
b) selective deletion of E3 genomic region consisting of ORF3, ORF4, ORF5, ORF6, and ORF7; and,
c) further comprising at least one ORF encoding a non-adenoviral anti-apoptotic protein.
2. The replication-incompetent adenovirus vector of claim 1 , wherein the anti-apoptotic protein is selected from the group consisting of a p53 inhibitor, Bcl-X L , BCL2, BCL2L1, BCL2A1, BAG1, TRAF1, BIRC3, BIRC5, BAK1, cIAP1, c-IAP2, XIAP, and API5.
3. The replication-incompetent adenovirus vector of claim 1 , which is a human serotype.
4. The replication-incompetent adenovirus vector of claim 1 , which has a serotype of a group selected from the group consisting of group A, group B, group C, group D, group E, and group F.
5. The replication-incompetent adenovirus vector of claim 1 , which has a serotype selected from the group consisting of Ad2, Ad3, Ad4, Ad5, Ad6, Ad7, Ad11, Ad20, Ad21, Ad22, Ad23, Ad24, Ad25, Ad26, Ad28, Ad34, Ad35, Ad40, Ad41, Ad48, Ad49, and Ad50.
6. The replication-incompetent adenovirus vector of claim 1 , which has a serotype selected from the group consisting of AdC1, AdC3, AdC6, AdC7, and AdC68.
7. The replication-incompetent adenovirus vector of claim 1 , comprising a deletion in E1 genomic region.
8. The replication-incompetent adenovirus vector of claim 1 , further comprising an ORF encoding an antigenic protein, wherein the antigenic protein is toxic to cell machinery when expressed by said replication-incompetent adenovirus vector.
9. An immunogenic composition comprising the replication-incompetent adenovirus vector of claim 1 .
10. A dosage unit of the an immunogenic composition of claim 9 , which comprises 10 8 to 10 11 adenoviral particles.
11. A packaging cell line comprising the replication-incompetent adenovirus vector of claim 1 .
12. The packaging cell line of claim 11 comprising HEK293 cells.