Influenza antigen delivery vectors and constructs
The present invention relates to fluorocarbon vectors for the delivery of influenza antigens to immunoresponsive target cells. It further relates to fluorocarbon vector-influenza antigen constructs and the use of such vectors associated with antigens as vaccines and immunotherapeutics in animals, including humans.
1. A fluorocarbon vector-antigen construct of structure C m F n —C y H x -(Sp)-R, wherein 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 a peptide consisting of SEQ ID NO: 1, 4, 17, 18, 19, 20, or 32.
2. The fluorocarbon vector-antigen construct of claim 1 , wherein R comprises multiple epitopes and/or fusion peptides.
3. A pharmaceutical composition comprising the fluorocarbon vector-antigen construct of claim 1 and one or more pharmaceutically acceptable carriers, excipients, diluents or adjuvants.
4. A pharmaceutical composition comprising the fluorocarbon vector-antigen construct of claim 1 formulated for parenteral, oral, ocular, rectal, nasal, transdermal, topical, or vaginal administration.
5. A pharmaceutical composition comprising the fluorocarbon vector-antigen construct of claim 1 , wherein the pharmaceutical composition is a liquid, emulsion, solid, aerosol or gas.
6. A pharmaceutical composition comprising the fluorocarbon vector-antigen construct of claim 1 in combination with an adjuvant, wherein the adjuvant is selected from the group consisting of:
a naturally or synthetically derived bacterial component, a Freund's adjuvant, a muramyldipeptide (MDP) derivative, CpG, a monophosphoryl lipid A, a saponin, an aluminium salt, a cytokine, an oil-in-water adjuvant, a water-in-oil adjuvant, an immunostimulating complex, a liposome, nano-particles, micro-particles, a bacterial toxin and a toxoid.
7. The pharmaceutical composition of claim 3 which comprises at least two vector-antigen constructs, the first construct comprising an influenza peptide sequence consisting of:
(SEQ ID NO: 1)
HMAIIKKYTSGRQEKNPSLRMKWMMAMKYPITADK
and the second construct comprising an influenza peptide sequence consisting of:
(SEQ ID NO: 17)
YITRNQPEWFRNVLSIAPIMFSNKMARLGKGYMFE.
8. The pharmaceutical composition of claim 7 comprising eight different vector-antigen constructs, each of which comprise an influenza peptide sequence consisting of:
(SEQ ID NO: 1)
HMAIIKKYTSGRQEKNPSLRMKWMMAMKYPITADK;
(SEQ ID NO: 4)
VAYMLERELVRKTRFLPVAGGTSSVYIEVLHLTQG;
(SEQ ID NO: 17)
YITRNQPEWFRNVLSIAPIMFSNKMARLGKGYMFE;
(SEQ ID NO: 18)
APIMFSNKMARLGKGYMFESKXMKLRTQIPAEMLA,
wherein X is R;
(SEQ ID NO: 19)
SPGMMMGMFNMLSTVLGVSILNLGQKKYTKTTY;
(SEQ ID NO: 20)
KKKSYINKTGTFEFTSFFYRYGFVANFSMELPSFG;
(SEQ ID NO: 32)
DQVRESRNPGNAEIEDLIFLARSALILRGSVAHKS;
or
(SEQ ID NO: 35)
DLEALMEWLKTRPILSPLTKGILGFVFTLTVPSER.
9. A method of treatment or immunization, the method comprising the step of administering the composition of claim 3 .
10. A method of stimulating an immune response, the method comprising administering the composition of claim 3 to an animal.
11. A method of stimulating an immune response, the method comprising administering the composition of claim 3 to a bird.
12. A method of stimulating an immune response, the method comprising administering the composition of claim 3 to a mammal.
13. A method of stimulating an immune response, the method comprising administering the composition of claim 3 to a human.
14. The method of claim 9 wherein the pharmaceutical composition is combined with anti-influenza therapy.
15. The method of claim 14 wherein the anti-influenza therapy is a neuraminidase inhibitor.
16. The method of claim 9 , further comprising contemporaneously or separately administering a haemagglutinin-containing influenza vaccine.
17. A method of preparing a prophylactic or therapeutic pharmaceutical product comprising combining the fluorocarbon construct of claim 1 with one or more pharmaceutically acceptable carriers, excipients, diluents, or adjuvants.
18. The method of claim 17 wherein the vaccine or product is for parenteral, mucosal, oral, nasal, topical, ocular, rectal, transdermal, or vaginal administration.
19. The pharmaceutical composition of claim 7 which comprises at least five different vector-antigen constructs.
20. The pharmaceutical composition of claim 19 which comprises six different vector-antigen constructs.
21. The pharmaceutical composition of claim 20 , wherein the six different vector-antigen constructs each comprise an influenza peptide sequence selected from the group consisting of SEQ ID NO: 1; SEQ ID NO: 4; SEQ ID NO: 17; SEQ ID NO: 18, wherein X is R; SEQ ID NO: 19; SEQ ID NO: 20; SEQ ID NO: 32; and SEQ ID NO: 35.
22. The pharmaceutical composition of claim 20 , wherein the six different vector-antigen constructs comprise an amino acid sequence consisting of SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 17, SEQ ID NO: 18, wherein X is R, SEQ ID NO: 32, or SEQ ID NO: 35.
23. A pharmaceutical composition comprising a first peptide consisting of the amino acid sequence:
HMAIIKKYTSGRQEKNPSLRMKWMMAMKYPITADK
(SEQ ID NO: 1)
and a second peptide consisting of the amino acid sequence:
(SEQ ID NO: 17)
YITRNQPEWFRNVLSIAPIMFSNKMARLGKGYMFE,
and one or more pharmaceutically acceptable carriers, excipients, diluents or adjuvants.
24. The pharmaceutical composition of claim 23 comprising six different peptides, each peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 1; SEQ ID NO: 4; SEQ ID NO: 17; SEQ ID NO: 18, wherein X is R; SEQ ID NO: 19; SEQ ID NO: 20; SEQ ID NO: 32; and SEQ ID NO: 35.
25. The pharmaceutical composition of claim 23 , comprising six different peptides, each peptide consisting of an amino acid sequence of SEQ ID NO: 1; SEQ ID NO: 4; SEQ ID NO: 17; SEQ ID NO: 18, wherein X is R; SEQ ID NO: 32; or SEQ ID NO: 35.
26. The fluorocarbon vector-antigen construct of claim 1 , wherein R is a peptide consisting of SEQ ID NO: 1.
27. The fluorocarbon vector-antigen construct of claim 1 , wherein R is a peptide consisting of SEQ ID NO: 4.
28. The fluorocarbon vector-antigen construct of claim 1 , wherein R is a peptide consisting of SEQ ID NO: 17.
29. The fluorocarbon vector-antigen construct of claim 1 , wherein R is a peptide consisting of SEQ ID NO: 18.
30. The fluorocarbon vector-antigen construct of claim 1 , wherein R is a peptide consisting of SEQ ID NO: 19.
31. The fluorocarbon vector-antigen construct of claim 1 , wherein R is a peptide consisting of SEQ ID NO: 20.
32. The fluorocarbon vector-antigen construct of claim 1 , wherein R is a peptide consisting of SEQ ID NO: 32.
33. The pharmaceutical composition of claim 3 further comprising a fluorocarbon vector-antigen construct of structure C m F n —C y H x -(Sp)-R, wherein 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 a peptide consisting of SEQ ID NO: 35.