Replicating recombinant adenovirus vectors, compositions, and methods of use thereof
AssigneesJanssen Vaccines & Prevention B.V., Beth Israel Deaconess Medical Center, Inc.
InventorsDan Barouch, Peter Abbink
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Abstract
Replicating recombinant adenovirus vectors derived from human adenovirus serotype 26 or human adenovirus serotype 35 are described. The replicating recombinant adenovirus vectors have attenuated replicative capacity as compared to that of the corresponding wild-type adenovirus. They can be used for stable expression of heterologous genes in vivo. Also described are compositions and methods of using these recombinant adenovirus vectors to induce an immune response in a subject, and vaccinate a subject against an immunogenic human immunodeficiency virus (HIV) infection.
Claims20
A replicating recombinant adenovirus vector, comprising a recombinant human adenovirus serotype 26 genome having:
- (a) a promoter operably linked to a heterologous nucleic acid sequence;
- (b) a functional E1 coding region that is sufficient for viral replication;
- (c) a deletion in the E3 coding region;
- and
- (d) a deletion in the E4 coding region, provided that E4 open reading frame 6/7 is not deleted.
A replicating recombinant adenovirus vector comprising a recombinant human adenovirus serotype 26 genome having:
- (a) a promoter operably linked to a heterologous nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:
- 48 or SEQ ID NO:
- 50;
- (b) a functional E1 coding region that is sufficient for viral replication encoding the amino acid sequences of SEQ ID NOs:
- 14-16;
- (c) a partially deleted E3 coding region consisting of the nucleotide sequence encoding the amino acid sequence of SEQ ID NO:
- 6;
- and
- (d) a partially deleted E4 coding region consisting of the nucleotide sequence encoding the amino acid sequence of SEQ ID NO:
- 22.
A method of producing an immune response in a human subject against an HIV infection, comprising:
- orally administering to the subject an immunogenically effective amount of a composition comprising a pharmaceutically acceptable carrier and a replicating recombinant adenovirus vector comprising a recombinant human adenovirus serotype 26 genome having:
- (a) a promoter operably linked to a heterologous nucleic acid sequence encoding the amino acid sequence of SEQ ID NO:
- 48 or SEQ ID NO:
- 50;
- (b) a functional E1 coding region that is sufficient for viral replication encoding the amino acid sequences of SEQ ID NOs:
- 14-16;
- (c) a partially deleted E3 coding region consisting of the nucleotide sequence encoding the amino acid sequence of SEQ ID NO:
- 6;
- and
- (d) a partially deleted E4 coding region consisting of the nucleotide sequence encoding the amino acid sequence of SEQ ID NO:
- 22,
- wherein the heterologous nucleic acid sequence is located between left ITR and 5′-end of the functional E1 coding region.
Dependencies are inferred from the claim text.