Chimeric adenoviral vectors
The present invention provides chimeric adenoviral vectors and methods for using the vectors to elicit an immune response to an antigen of interest.
1. An immunogenic composition, said composition comprising:
(a) a chimeric adenoviral expression vector comprising a promoter operably linked to a nucleic acid encoding a heterologous polypeptide, wherein the heterologous polypeptide is an human papilloma virus (HPV) polypeptide or herpes simplex virus (HSV) polypeptide;
(b) a non-specific immune response enhancer selected from dsRNA and a dsRNA mimetic; and
(c) a pharmaceutically acceptable carrier.
2. The composition of claim 1 , wherein the promoter is a CMV promoter.
3. The composition of claim 1 , wherein the ds RNA mimetic is poly I:C.
4. The composition of claim 1 , wherein the non-specific immune response enhancer is formulated to be administered within 48 hours of the administration of the chimeric adenoviral expression vector.
5. A method for eliciting an immune response, the method comprising administering to a mammalian subject
(a) a chimeric adenoviral expression vector comprising a promoter operably linked to a nucleic acid encoding a heterologous polypeptide, wherein the heterologous polypeptide is an human papilloma virus (HPV) polypeptide or herpes simplex virus (HSV) polypeptide;
(b) a non-specific immune response enhancer selected from dsRNA and a dsRNA mimetic, wherein the immune response is directed against the heterologous polypeptide.
6. The method of claim 5 , wherein the promoter is selected from the group consisting of the: CMV promoter and the human beta actin promoter.
7. The method of claim 5 , wherein the dsRNA mimetic is polyI:C.
8. The method of claim 5 , wherein the a non-specific immune response enhancer is administered within 48 hours of the administration of the chimeric adenoviral expression vector.
9. The immunogenic composition of claim 1 , wherein the heterologous polypeptide is a herpes simplex virus polypeptide.
10. The immunogenic composition of claim 1 , wherein the composition is formulated for oral, intranasal, or mucosal administration.
11. The immunogenic composition of claim 1 , wherein the composition is formulated for vaginal administration.
12. The method of claim 5 , wherein the heterologous polypeptide is a herpes simplex virus polypeptide.
13. The method of claim 5 , wherein the route of administration is vaginal.
14. The immunogenic composition of claim 1 , wherein the non-specific immune response enhancer is dsRNA, and wherein the chimeric adenoviral vector further comprises a nucleic acid sequence encoding the dsRNA.
15. The immunogenic composition of claim 14 , wherein the nucleic acid sequence encoding the dsRNA is operably linked to a second promoter.
16. The method of claim 5 , wherein the non-specific immune response enhancer is dsRNA, and wherein the chimeric adenoviral vector further comprises a nucleic acid sequence encoding the dsRNA.
17. The method of claim 16 , wherein the nucleic acid sequence encoding the dsRNA is operably linked to a second promoter.