Compositions and methods for alphavirus vaccination
Compositions of a recombinant adenovirus based vector vaccine containing one or more alphavirus antigen genes are disclosed herein. Methods for constructing and producing such vaccines and methods of using these vaccines to generate broad based immune responses against alphaviruses are also described. Compositions described herein allow for vaccinations in individuals with preexisting immunity to adenovirus.
1. A composition comprising a replication defective adenovirus 5 (Ad5) vector wherein the Ad5 vector comprises an E1 gene region deletion and E2b gene region deletion, and wherein the Ad5 vector further comprises a sequence encoding an antigen, wherein the antigen has at least 85% sequence identity to SEQ ID NO:2 or SEQ ID NO:5.
2. The composition of claim 1 , wherein the antigen is SEQ ID NO:2.
3. The composition of claim 1 , wherein the sequence encoding the antigen comprises a plurality of gene inserts each corresponding to a target antigen, wherein each gene insert is separated by a nucleic acid sequence encoding a self-cleaving 2A peptide.
4. The composition of claim 3 , wherein the self-cleaving 2A peptide is a Porcine teschovirus -1 2A peptide or a Thosea asigna virus 2A peptide.
5. The composition of claim 1 , wherein the replication defective Ad5 vector further comprises a deletion in an E3 gene region, E4 gene region, or any combination thereof.
6. The composition of claim 1 , wherein the replication defective Ad5 vector further comprises an element to increase an expression of the alphavirus target antigen, wherein the element comprises an internal ribosome binding site, a constitutive promoter, and inducible promoter, a transcription enhancer or combinations thereof.
7. The composition of claim 1 , wherein the replication defective Ad5 vector further comprises a nucleic acid sequence encoding a protein that increases alphavirus target antigen immunogenicity wherein the sequence is SEQ ID NO: 71.
8. The composition of claim 1 , wherein the composition or the replication defective Ad5 vector further comprises a sequence encoding a costimulatory molecule or an immunological fusion partner.
9. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable carrier.
10. An isolated cell comprising the composition according to the pharmaceutical composition of claim 9 .
11. The cell of claim 10 , wherein the cell is a dendritic cell (DC).
12. A method of generating an immune response against an alphavirus target antigen in a subject, comprising: administering to the subject a composition according to claim 1 .
13. A method of preventing a Chikungunya virus infection in a subject, the method comprising administering to the subject a composition comprising the composition of claim 1 .
14. The method of claim 13 , wherein the subject has preexisting immunity to an adenovirus or an adenovirus vector.
15. The method of claim 13 , wherein the administering to the subject comprises 1×10 9 to 5×10 12 virus particles per dose.
16. The composition of claim 6 , wherein the transcription enhancer is a Rous sarcoma virus (RSV) enhancer.
17. The composition of claim 6 , wherein the element does not contain a palindromic sequence.