Simian adenovirus and hybrid adenoviral vectors
Recombinant adenoviral vectors, immunogenic compositions thereof and their use in medicine, and methods for generating recombinant adenoviral vectors are provided. In particular, the an adenovirus vector having a capsid derived from chimpanzee adenovirus AdY25, wherein the capsid encapsidates a nucleic acid molecule comprising an exogeneous nucleotide sequence of interest are provided.
1. A method of treating a cancer in a subject using immunotherapy, said immunotherapy comprising:
directly administering to the cancer an adenovirus comprising a capsid comprising: one or more capsid proteins from chimpanzee adenovirus AdY25 which encapsidates a nucleic acid molecule comprising an exogeneous nucleotide sequence of interest encoding an antigen specific to the cancer operably linked to expression control sequences and an adenoviral packaging signal sequence; and
allowing sufficient time to elicit an immune response in the subject to treat the cancer.
2. The method of claim 1 , wherein the subject is a human subject.
3. The method of claim 1 , wherein the adenovirus comprises an AdY25 genome that lacks a functional E1 locus.
4. The method of claim 1 , wherein the adenovirus comprises an AdY25 genome that lacks an E3 locus.
5. The method of claim 1 , wherein the adenovirus comprises an AdY25 genome with an E4 locus wherein at least one of the E4 open reading frames (ORF) is heterologous.
6. The method of claim 5 , wherein the entire E4 locus is heterologous.
7. The method of claim 6 , wherein the E4 ORF is E4Orf6 from AdHu5.
8. The method of claim 5 , wherein the adenovirus has an E4 locus that comprises E4Orf1, E4Orf2 and E4Orf3 from AdY25 and E4Orf4, E4Orf6 and E4Orf6/7 from AdHu5.
9. The method of claim 1 , wherein the cancer antigen is a self-antigen.
10. The method of claim 9 , wherein the self antigen is GD2 or ErbB2.
11. The method of claim 1 , wherein the exogenous nucleotide sequence of interest further encodes a tumor associated antigen (TAA) from a pathogen involved in cancer immunopathogenesis.
12. The method of claim 11 , wherein the antigen from a pathogen involved in cancer immunopathogenesis is from human papilloma virus (HPV), hepatitis B virus (HBV) or Epstein Barr virus (EBV).
13. The method of claim 1 , wherein the one or more capsid proteins from the AdY25 are 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.
14. The method of claim 1 , wherein the administering the vaccine comprises parenteral administration of the adenovirus vector to the subject.
15. The method of claim 1 , wherein the exogenous nucleotide sequence of interest further encodes a TAA.