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 composition comprising:
a fluorocarbon vector-antigen construct of 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, Sp is an optional chemical spacer moiety, and R is an immunogenic peptide comprising an antigen selected from the group consisting of a viral antigen, a bacterial antigen, a parasitic antigen, and a cancer antigen, wherein said peptide has a naturally occurring sequence with optionally modified N or C terminal amino acid residues; and
one or more pharmaceutically acceptable carriers, excipients, diluents or adjuvants.
2. The composition of claim 1 , wherein the fluorocarbon vector-antigen construct has a structure
3. The composition of claim 1 , wherein the fluorocarbon vector-antigen construct has a structure
4. The composition of claim 1 , wherein the fluorocarbon vector-antigen construct has a structure
5. The composition of claim 1 , wherein R comprises one or more epitopes from a viral protein.
6. A fluorocarbon vector-antigen construct of 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 comprises one or more epitopes from a human immunodeficiency virus protein.
7. The composition of claim 1 , wherein R is a peptide consisting of between 7 to 70 amino acids.
8. The composition of claim 1 , wherein R is a peptide comprising a B cell binding epitope.
9. The composition of claim 1 , wherein R comprises more than two or more overlapping epitopes.
10. The fluorocarbon vector-antigen construct of claim 6 where R is an HIV epitope.
11. A fluorocarbon vector-antigen construct of 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 a peptide selected from SEQ ID Nos 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 or combinations thereof.
12. The fluorocarbon vector-antigen construct of claim 6 wherein R is one or more HIV env epitopes.
13. The fluorocarbon vector-antigen construct of claim 10 where R is an HIV env epitope peptide with an amino acid sequence of NNTRKRIRIQRGPGRAFVTIGK-NH 2 (SEQ ID NO: 38).
14. The composition of claim 1 , wherein the fluorocarbon vector is non-covalently associated with an antigen.
15. The composition of claim 1 , wherein R comprises multiple epitopes and/or fusion peptides.
16. The composition of claim 1 formulated for parenteral, oral, ocular, rectal, nasal, transdermal, topical, or vaginal administration.
17. The composition of claim 1 , wherein the composition is a liquid, solid, aerosol or gas.
18. The composition of claim 1 comprising an adjuvant selected from the group consisting of muramyldipeptide (MDP) derivatives, CpG, monophosphoryl lipid A, oil in water adjuvants, water-in-oil adjuvants, aluminum salts, immunostimulating complex (ISCOMs), liposomes, microparticules, saponins, cytokines, and bacterial toxins and toxoids.
19. A composition comprising:
a fluorocarbon vector-antigen construct of structure C m F n− —C y H x -(Sp)-R, where m=3to 30, n<=2m+1, y=0 to 15, x<=2y, (m+y)=3-30and Sp is an optional chemical spacer moiety and R is an immunogenic peptide comprising one or more epitopes from an influenza virus protein; and
one or more pharmaceutically acceptable carriers, excipients, diluents or adjuvants.
20. The composition of claim 19 formulated for parenteral, oral, ocular, rectal, nasal, transdermal, topical or vaginal administration.
21. The composition of claim 19 , wherein the composition is a liquid, solid, aerosol or gas.
22. The composition of claim 19 comprising an adjuvant selected from the group consisting of muramyldipeptide (MDP) derivatives, CpG, monophosphoryl lipid A, oil in water adjuvants, water-in-oil adjuvants, aluminum salts, immunostimulating complex (ISCOMs), liposomes, microparticules, saponins, cytokines, and bacterial toxins and toxoids.
23. The composition of claim 1 , wherein the immunogenic peptide defines a T-cell epitope.
24. A composition comprising:
a fluorocarbon vector-antigen construct of 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, Sp is an optional chemical spacer moiety, and R is an immunogenic peptide defining a T-cell epitope, wherein said peptide has a naturally occurring sequence with optionally modified N or C terminal amino acid residues; and
one or more pharmaceutically acceptable carriers, excipients, diluents or adjuvants.
25. The composition of claim 24 , wherein the fluorocarbon vector-antigen construct has a structure
26. The composition of claim 24 , wherein the fluorocarbon vector-antigen construct has a structure
27. The composition of claim 24 , wherein the fluorocarbon vector-antigen construct has a structure
28. The composition of claim 24 , wherein the epitope is from a viral protein.