Patent EA-004797-B1 (EA)
Title: Immunogenic liposome compositions
Inventor: FUJII GARY
IPC: C07K14/18
Filed: 1999-09-22
Abstract: 1. An immunogenic unilamellar liposome composition comprising: vesicle-forming lipids; and an antigenic construct comprising one or more antigenic determinants and a hydrophobic domain, wherein the hydrophobic domain has a surface area greater than 500 angstrom <2> and is associated with the membrane of said unilamellar liposome composition, and wherein the immunogenic composition elicits a response associated with cell mediated immunity. 2. The immunogenic liposome composition of claim 1 further comprising one or more adjuvants. 3. The immunogenic liposome composition of claim 1 wherein the antigenic construct is recombinantly produced, chemically synthesized or a combination thereof. 4. The immunogenic liposome composition of claim 1 wherein the hydrophobic domain is a peptide. 5. The immunogenic liposome composition of claim 4 wherein the hydrophobic domain consists of from about 15 to about 500 ammo acid residues. 6. The immunogenic liposome composition of claim 5 wherein me hydrophobic domain comprises one or more amino acids selected from the group consisting of Ala, Asn, Cys, Gln, Gly, His, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr and Val. 7. The immunogenic liposome composition of claim 1, wherein the antigenic determinant is derived from an antigen selected from the group consisting of HSV gB or gD, HIV gp120, CMV gB, HCV E2, INFV HA or NA, H, influenzae P5 or P6, fimbrial protein and Protein D. 8. The immunogenic liposome composition of claim 1 wherein the antigenic construct further comprises a linker region linking the antigenic determinants with the hydrophobic domain. 9. The immunogenic liposome composition of claim 1 wherein the linker region is a peptide. 10. The immunogenic liposome composition of claim 9 wherein the peptide linker region consists of from 1 to about 200 ammo acid residues. 11. The immunogenic liposome composition of claim 10 wherein the ammo acid residues are selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Glu, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, The, Trp, Tyr and Val. 12. The immunogenic liposome composition of claim 1 wherein the antigenic construct is a fusion protein. 13. The immunogenic liposome composition of claim 9 wherein the antigenic construct is a fusion protein. 14. Use of an immunogenically effective amount of the composition of claim 1 for inducing an immunogenic response in a host animal. 15. Use of an immunogenically effective amount of the composition of claim 2 for inducing an immunogenic response in a host animal. 16. The use of claim 14 wherein the host animal is a mammal. 17. The use of claim 16 wherein the mammal is a human. 18. The use of claim 14 wherein the animal is a bird. 19. The use of claim 17, wherein the antigenic determinant is selected from the group consisting of HSV gB or gD, HIV gp120, CMV gB, HCV E2, INFV HA or NA, H. influenzae P5 or P6, fimbrial protein and Protein D. 20. A vaccine composition comprising an effective amount of a composition of claim 1 and a pharmaceutically acceptable carrier. 21. The vaccine composition of claim 20 further comprising one or more adjuvants. 22. A DNA cassette for insertion into an expression vector comprising sequences which encode an, immunogenic fusion protein, said protein comprising: a hydrophobic domain having a surface area greater than 500 angstrom 2, and an antigenic construct comprising one or more antigenic determinants. 23. The DNA cassette of claim 22, wherein me antigenic determinant is derived from an antigen selected from the group consisting of HSV gB or gD, HIV gp120, CMV gB, HCV E2, INFV HA or NA, H. influenzae P5 or P6, fimbrial protein and Protein D. 24. The DNA cassette of claim 22, wherein the hydrophobic domain is a peptide consisting of from about 15 to about 500 ammo acid residues. 25. The DNA cassette of claim 24, wherein the peptide comprises one or more amino acids selected from the group consisting of Ala, Asn, Cys, Gln, Gly, His, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr and Val. 26. The DNA cassette of claim 21, wherein the fusion, protein further comprises a linker region linking the antigenic determinant and the hydrophobic domain. 27. The DNA cassette of claim 26, wherein the linking region consists of 1 to about 200 amino acid residues. 28. The DNA cassette of claim 27, wherein the amino acid residues are selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Glu, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr and Val. 29. A vector comprising the DNA cassette of claim 22. 30. A method of making an immunogenic unilamellar liposome composition comprising: expressing a gene that encodes a fusion protein comprising a hydrophobic domain having a surface area greater than 500 angstrom 2, and an antigenic construct comprising one or more antigenic determinants; dissolving vesicle-forming lipids and the fusion protein in a suitable organic solvent; forming a lipid film or spray dried powder by evaporating the organic solvent; hydrating the lipid film or powder; and dispersing the hydrated lipid film or powder to form an immunogenic unilamellar liposome composition. 31. A method of making an immunogenic unilamellar liposome composition comprising: expressing a gene that encodes a fusion protein comprising a hydrophobic domain having a surface area greater than 500 angstrom 2, and an antigenic construct comprising one or more antigenic determinants; dissolving the fusion protein in an aqueous buffer; hydrating either lipid powders or lipid films with the buffer containing the fusion protein; and dispersing the lipid powders or films to form an immunogenic unilamellar liposome composition. 32. A method of making an immunogenic unilamellar liposome composition comprising: expressing a gene that encodes a fusion protein comprising a hydrophobic domain having a surface area greater than 500 angstrom 2, and an antigenic construct comprising one or more antigenic determinants; dissolving the fusion protein in an aqueous buffer; and adding me fusion protein to pre-formed unilamellar liposomes to form an immunogenic unilamellar liposome composition. 33. An immunogenic unilamellar composition comprising an antigenic construct comprising one or more antigenic determinants and a hydrophobic domain having a surface area greater than 500 angstrom 2; and a pharmaceutically acceptable carrier. 34. The immunogenic composition of claim 33 wherein the antigenic construct further comprises a linker region linking the antigenic determinants with the hydrophobic domain. 35. The immunogenic composition of claim 33 further comprising one or more adjuvants. 36. An immunogenic lipid emulsion composition comprising: oil; vesicle-forming lipids; and an antigenic construct comprising one or more antigenic determinants and a hydrophobic domain that has a surface area greater than 500 angstrom 2. 37. The composition of claim 36 wherein the antigenic construct is a fusion protein. 38. The immunogenic liposome composition of claim 1 wherein the response associated with cell mediated immunity comprises a delayed hypersensitivity response. 39. The immunogenic liposome composition of claim 1 wherein the lipids comprising the liposome are in fluid phase at body temperature. 40. The immunogenic liposome composition of claim 1 wherein the lipids contain no more than about 10% cholesterol. 41. The vaccine composition of claim 20 wherein the lipids comprising the liposome are in fluid phase at body temperature. 42. The vaccine composition of claim 20 wherein the lipids contain no more than about 10% cholesterol. 43. The vaccine composition of claim 20 wherein the antigenic construct is recombinantly produced, chemically synthesized or a combination thereof. 44. The vaccine composition of claim 20 wherein the hydrophobic domain is a peptide. 45. The vaccine composition of claim 44 wherein the hydrophobic domain consists of from about 15 to about 500 amino acid residues. 46. The vaccine composition of claim 44 wherein the hydrophobic domain comprises one or more amino acids selected from the group consisting of Ala, Asn, Cys, Gln, Gly, His, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr and Val. 47. The vaccine composition of claim 20, wherein the antigenic determinant is derived from an antigen selected from the group consisting of HSV gB or gD, HIV gp120, CMV gB, HCV E2, INFV HA or NA, H. influenzae P5 or P6, fimbrial protein and Protein D. 48. The vaccine composition of claim 20 wherein the antigenic construct further comprises a peptide linker region linking the antigenic determinants with the hydrophobic domain. 49. The vaccine composition of claim 48 wherein the peptide linker region consists of from 1 to about 200 ammo acid residues. 50. The vaccine composition of claim 49 wherein the amino acid residues are selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Glu, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr and Val. 51. The composition of claim 36 wherein the lipids are in fluid phase at body temperature. 52. The composition of claim 36 wherein the lipids contain no more than about 10% cholesterol. 53. The composition of claim 36 wherein the antigenic construct is recombinantly produced, chemically synthesized or a combination thereof. 54. The composition of claim 36 wherein the hydrophobic domain is a peptide. 55. The composition of claim 54 wherein the hydrophobic domain consists of from about 15 to about 500 amino acid residues. 56. The composition of claim 55 wherein the hydrophobic domain comprises one or more amino acids selected from me group consisting of Ala, Asn, Cys, Gln, Gly, His, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr and Val. 57. The composition of claim 36, wherein the antigenic determinant is derived from an antigen selected from the group consisting of HSV gB or gD, HIV gp120, CMV gB, HCV E2, INFV HA or NA, H. influenzae P5 or P6, fimbrial protein and Protein D. 58. The composition of claim 36 wherein the