Simian adenovirus and hybrid adenoviral vectors
View Patent ↗The present invention provides recombinant adenoviral vectors, immunogenic compositions thereof and their use in medicine, and methods for generating recombinant adenoviral vectors. In particular, the present invention provides an adenovirus vector comprising a capsid derived from chimpanzee adenovirus AdY25, wherein said capsid encapsidates a nucleic acid molecule comprising an exogeneous nucleotide sequence of interest.
1. An adenovirus vector comprising a capsid, wherein said capsid comprises one or more capsid proteins from chimpanzee adenovirus AdY25 and encapsidates a nucleic acid molecule comprising an exogenous nucleotide sequence of interest operably linked to expression control sequences which direct the expression thereof in an animal cell and an adenoviral packaging signal sequence, and wherein the nucleotide sequence that encodes the wild-type chimpanzee adenovirus AdY25 is SEQ ID No. 1.
2. The vector of claim 1 wherein said vector comprises an AdY25 genome that lacks a functional E1 locus.
3. The vector of claim 1 wherein said vector comprises an AdY25 genome that lacks an E3 locus.
4. The vector of claim 1 wherein the vector comprises an AdY25 genome wherein at least one of the E4 open reading frame (Orf) is heterologous.
5. The vector of claim 4 wherein the vector lacks a native E4 locus and the at least one E4Orf is the entire E4 locus.
6. The vector of claim 5 wherein the E4Orf6 open reading frame is from AdHu5.
7. The vector of claim 4 having an E4 locus that comprises E4Orf1, E4Orf2, and E4Orf3 from AdY25 and E4Orf4, Orf6 and Orf6/7 from AdHu5.
8. The vector of claim 1 wherein the exogenous nucleotide sequence of interest encodes a protein or a polypeptide.
9. The vector of claim 8 wherein the protein or the polypeptide is selected from the group comprising an antigen, a molecular adjuvant, an immunostimulatory protein or a recombinase.
10. The vector of claim 9 , wherein said antigen is Ag85A from Mycobacterium tuberculosis.
11. The vector of claim 1 wherein said exogenous nucleotide sequence of interest is an miRNA or an immunostimulatory RNA sequence.
12. The vector of claim 1 wherein said capsid comprises one or more capsid proteins selected from the group consisting of:
(a) an AdY25 hexon protein comprising the amino acid sequence of SEQ ID NO. 2:
(b) an AdY25 penton protein comprising the amino acid sequence of SEQ ID NO. 3; and
(c) an AdY25 fibre protein comprising the amino acid sequence of SEQ ID NO. 4.
13. An isolated nucleic acid molecule having a sequence identical to SEQ ID NO. 1 over its entire length.