Patent EA-005313-B1 (EA)
Title: Method for obtaining antigenic structures enhancing specific cross reactivity
Inventor: CRUZ RICONDO LUIS JAVIER
IPC: A61K47/48
Filed: 2001-11-01
Abstract: 1. Method for obtaining antigenic structures able to enhance the specific cross reactivity comprising the steps: A) selection of the epitope of interest; B) obtaining of dendrimeric structures with the epitopes selected in (A), using a method of synthesis selected from the following group: 1) synthesis on a nucleus of aspartic acid or lysine; 2) synthesis on a nucleus of organic molecules and 3) direct coupling of peptides on a dendrimeric nucleus, the B and T-cell epitopes can be mixed on the same nucleus; C) conjugation of one or various dendrimeric structures obtained in (B), to one or various carrier molecules using a method of coupling selected from the group consisting in: 1) conjugation using glutaraldehyde, 2) using succinic anhydride, 3) using the ester of the beta -maleimidopropionic-N-hidroxisucci-nimidic acid (MPS), and 4) any method avoiding the use of spacer agents with aromatic side chains; D) mixture of conjugates obtained in the step (C) including the addition of the CD4-binding peptide or a conjugate containing it; and E) adjuvation of the resulting formulation in alum or a any other convenient adjuvant. 2. Method according to claim 1, wherein peptides contained in the structures obtained from step (B) belong to regions from the Human Immunodeficiency virus type 1 or 2. 3. Method according to claim 2, wherein peptides contained in the structures obtained from the step (B) belong to variable regions from the Human Immunodeficiency virus type 1 or 2. 4. Method according to claim 3, wherein peptides contained in the structures obtained from the step (B) belong to the third variable region (V3) from the Human Immunodeficiency Virus 1 or 2. 5. Method for according to claim 1, wherein peptides contained in the structures obtained from the step (B) belong to the Hepatitis B Virus. 6. Method according to claim 1, wherein peptides contained in the structures obtained from the step (B) belong to the Hepatitis C Virus. 7. Method according to claim 1, wherein peptides contained in the structures obtained from the step (B) belong to Dengue Virus. 8. Method according to claim 1, wherein the oligomers contained in the structures obtained from the step (B) belong to polysaccharidic regions from Neisseria meningitidis. 9. Method according to claim 1, wherein peptides contained in the structures obtained from the step (B) are mimetic peptides of antigenic polyssacharides. 10. Method according to claim 1, wherein peptides contained in the structures obtained from the step (B) belong to antigenic regions from a microorganism or a pathogen. 11. Method according to claim 1, wherein peptides contained in the structures obtained from the step (B) belong to self-antigens. 12. Method according to claim 11, wherein peptides contained in the structures obtained from the step (B) belong to the Gonadotropine Releasing Hormone. 13. Method according to claim 1, wherein the carrier molecule from the step (C) is the Hepatitis B surface antigen, HBsAg. 14. Method according to claim 1, wherein the carrier molecule from the step (C) is the p64K protein from Neisseria meningitidis. 15. Method according to claim 1, wherein the carrier molecule from the step (C) is the core protein from the Human Inmunodeficiency Virus. 16. Method according to claim 1, wherein the-carrier molecule from the step (C) is the hepatitis b core antigen or the Hepatitis C core antigen. 17. Method according to claim 1, wherein the carrier molecule from the step (C) is a polysaccharide. 18. Method according to claim 17, wherein the carrier molecule from the step (C) is a dextran. 19. Method according to claim 1, wherein the carrier molecule and the dendrimeric structure from the step (C) are coupled covalently, electrostatically or by hydrophobicity. 20. Antigenic structure able to enhance the specific cross reactivity comprising dendrimeric antigenic epitopes coupled to carrier proteins. 21. Antigenic structure according to claim 20 wherein the epitopes from the dendrimeric region have peptidic or oligosaccharidic nature. 22. Antigenic structure according to claim 21 wherein the epitopes of peptidic nature are peptidic consensus of variable regions selected from subtypes, subgroups, serotypes or other kind of associations. 23. Antigenic structure according to claim 21 wherein the epitopes of peptidic nature are peptidic libraries from peptidic sequences selected from microorganisms or mimetic peptides. 24. Antigenic structure according to claims 21 to 23 wherein the epitopes from the dendrimeric peptidic regions belong to the Human Immunodeficiency Virus 1 or 2. 25. Antigenic structure according to claims 24 wherein the epitopes from the dendrimeric peptidic regions belong to variable regions from the Human Immunodeficiency Virus 1 or 2. 26. Antigenic structure according to claim 25 wherein the epitopes from the dendrimeric peptidic regions belong to the V3 variable region from the Human Immunodeficiency Virus 1 or 2. 27. Antigenic structure according to claims 21 to 23 wherein the epitopes from the dendrimeric peptidic regions belong to regions from the Hepatitis B Virus. 28. Antigenic structure according to claims 21 to 23 wherein the epitopes from the dendrimeric peptidic regions belong to regions from the Hepatitis C Virus. 29. Antigenic structure according to claims 21 to 23 wherein the epitopes from the dendrimeric peptidic regions belong to regions from Dengue Virus. 30. Antigenic structure according to claim 21 wherein the epitopes from the dendrimeric peptidic regions belong to polysaccharidic antigens from Neisseria meningitidis. 31. Antigenic structure according to claims 21 to 23 wherein the epitopes from the dendrimeric peptidic regions are mimetic peptides from polysaccharidic or proteic antigens. 32. Antigenic structure according to claims 21 to 23 wherein the epitopes from the dendrimeric peptidic regions belong to microorganisms or pathogens. 33. Antigenic structure according to claims 21 to 23 wherein the epitopes from the dendrimeric peptidic regions belong to self-antigens. 34. Antigenic structure according to claims 21 to 23 wherein the epitopes from the dendrimeric peptidic regions belong to the Gonadotropine Releasing Hormone. 35. Antigenic structure according to claim 20 wherein the carrier molecule is the Hepatitis B Surface Antigen, HBsAg. 36. Antigenic structure according to claim 20 wherein the carrier molecule is the p64K protein from Neisseria meningitidis. 37. Antigenic structure according to claim 20 wherein the carrier molecule is the HIV nucleocapside antigen. 38. Antigenic structure according to claim 20 wherein the carrier molecule is the HBV nucleocapside antigen (HBcAg). 39. Antigenic structure according to claim 20 wherein the carrier molecule is a polysaccharide. 40. Antigenic structure according to claim 39 wherein the carrier molecule is a dextran. 41. Use of the antigenic structure according to claims 20 to 40 in a diagnostic system. 42. Use of the antigenic structure according to claims 20 to 40 in preventive and therapeutic vaccines. 43. Vaccine formulation comprising the antigenic structure of claims 20 to 40 adsorbed or adjuvated conveniently. 44. Vaccine formulation according to claim 43 for systemic or mucosal use. 45. Use of vaccine formulations of claims 43 and 44 to prevent infectious diseases, autoimmunity or cancer. 46. Use of vaccine formulations of claims 43 and 44 to treat infectious diseases, autoimmunity or cancer.