Antigen delivery vectors and constructs
The present invention relates to fluorocarbon vectors for the delivery of antigens to immunoresponsive target cells. It further relates to fluorocarbon vector-antigen constructs and the use of such vectors associated with antigens as vaccines and immunotherapeutics in animals.
1. A multi-component pharmaceutical composition configured for intracellular delivery of T cell epitopes to induce a cell-mediated immune response, the pharmaceutical composition comprising:
two to about 20 different types of fluorocarbon peptide constructs, wherein each different type of fluorocarbon peptide construct comprises:
a fluorocarbon chain from 3 to 30 carbon atoms, wherein one or more fluorine moieties is optionally substituted with chlorine, bromine or iodine or a methyl group; and,
a peptide comprising one or more CD8+T cell epitopes including at least two MHC class I or II epitopes, the peptide being coupled to the fluorocarbon vector via either an N-terminus or C-terminus of the peptide and the fluorocarbon vector;
wherein the fluorocarbon peptide constructs are comprised within micelles, each different type of fluorocarbon peptide construct comprises a different peptide sequence, and the fluorocarbon chain enhances CD8+T cell response against the peptide; and,
one or more pharmaceutical acceptable carriers, excipients, diluents or adjuvants.
2. The composition of claim 1 wherein the fluorocarbon peptide construct is according to structure
where Sp is an optional chemical spacer moiety and R is the peptide.
3. The composition of claim 1 wherein the fluorocarbon peptide construct is according to structure
where Sp is an optional chemical spacer moiety and R is the peptide.
4. The composition of claim 1 wherein the fluorocarbon peptide construct is according to structure
where Sp is an optional chemical spacer moiety and R is the peptide.
5. The composition of claim 1 wherein the peptide comprises one or more immunogenic epitopes from a viral protein.
6. The composition of claim 1 wherein the peptide comprises one or more immunogenic epitopes from an influenza or hepatitis B virus protein.
7. The composition of claim 1 wherein the peptide comprises between 7 to 70 amino acids.
8. The composition of claim 1 wherein the peptide comprises two or more overlapping T cell epitopes.
9. The composition of claim 1 wherein the peptide is an HIV epitope.
10. The composition of claim 1 wherein the peptide comprises multiple overlapping viral T cell epitopes and/or fusion peptides.
11. The composition of claim 1 , wherein the fluorocarbon peptide construct is according to structure C m F n -C y H x -Sp)-R, where m=3 to 30, n<=2m+1, y=0 to 15, x<=2y, (m+y)=3−30 and Sp is an optional chemical spacer moiety and R is the peptide.
12. A combination of different types of fluorocarbon peptide constructs configured for intracellular delivery of T cell epitopes to induce a cell-mediated immune response, each different type of fluorocarbon peptide construct comprising:
a fluorocarbon chain from 3 to 20 carbon atoms, wherein one or more fluorine moieties is optionally substituted with chlorine, bromine or iodine or a methyl group, and
an in vivo immunogenic peptide of between 7 to 70 amino acids in length, comprising one or more CD8+T cell epitopes, at least two MHC class I or MHC class II epitopes, and being covalently linked via either an N-terminus or C-terminus terminal lysine to the fluorocarbon chain,
wherein each different type of fluorocarbon peptide construct comprises a different in vivo immunogenic peptide sequence and the fluorocarbon chain enhances CD8+T cell response against the peptide; and,
wherein the combination of different types of the fluorocarbon constructs is lyophilized.
13. The fluorocarbon peptide construct of claim 12 , wherein the peptide is between 15 to 35 amino acids in length.
14. The fluorocarbon peptide construct of claim 12 , wherein the fluorocarbon peptide construct is according to structure C m F n —C y H x -Sp-R, where m=3 to 30, n<=2m+1, y=0 to 15, x<=2y, (m+y)=3−30 and Sp is an optional chemical spacer moiety and R is the peptide.
15. The fluorocarbon peptide construct of claim 12 , wherein the fluorocarbon peptide construct is according to structure
where Sp is an optional chemical spacer moiety and R is the peptide.
16. The fluorocarbon peptide construct of claim 12 , wherein the peptide comprises one or more epitopes from an influenza or hepatitis B virus protein.
17. A multi-component pharmaceutical composition configured for intracellular delivery of T cell epitopes to induce a cell-mediated immune response, the pharmaceutical composition comprising:
two to about 20 different types of fluorocarbon peptide constructs, wherein each different type of fluorocarbon peptide construct comprises:
a fluorocarbon chain from 3 to 30 carbon atoms, wherein one or more fluorine moieties is substituted with chlorine, bromine or iodine or a methyl group; and,
a peptide comprising one or more CD8+T cell epitopes including at least two MHC class I or II epitopes, the peptide being coupled to the fluorocarbon vector via either an N-terminus or C-terminus of the peptide and the fluorocarbon vector;
wherein the fluorocarbon peptide constructs are comprised within micelles, and wherein each different type of fluorocarbon peptide construct comprises a different peptide sequence, and the fluorocarbon chain enhances CD8+T cell response against the peptide; and,
one or more pharmaceutical acceptable carriers, excipients, diluents or adjuvants.
18. The composition of claim 17 , wherein the peptide comprises multiple overlapping viral T cell epitopes and/or fusion peptides.
19. The composition of claim 17 wherein the peptide comprises between 7 to 70 amino acids.