Induction of mucosal tolerance to antigens
The present invention relates to the induction of tolerance to antigens, by mucosal, preferably oral delivery of the antigen in combination with an immunomodulating compound producing micro-organism. More specifically, the invention relates to the induction of Foxp3 + and/or IL-10 and/or TGF-β producing regulatory T-cells, capable of suppressing undesired immune responses toward an antigen, by oral delivery of said antigen in combination with an immunosuppressing cytokine secreting micro-organism.
1. A medicament, nutraceutical, or medical food for treating and/or alleviating type I diabetes or for inducing immune tolerance to type I diabetes comprising a beta cell autoantigen in type I diabetes and an IL-10 secreting Lactococcus lactic.
2. The medicament, nutraceutical, or medical food according to claim 1 , wherein said autoantigen is pro-insulin insulin, an immuno-dominant peptide of insulin or pro-insulin, or a combination thereof.
3. The medicament, nutraceutical, or medical food according to claim 1 , wherein said autoantigen is secreted by an autoantigen secreting Lactococcus lactis.
4. The medicament, nutraceutical, or medical food according to claim 1 , wherein said medicament, nutraceutical, or medical food is for mucosal delivery to a subject.
5. A composition comprising a beta cell autoantigen in type I diabetes and an IL-10 secreting Lactococcus lactis.
6. The composition according to claim 5 , wherein said autoantigen is pro-insulin, insulin, an immuno-dominant peptide of insulin or pro-insulin, or a combination thereof.
7. The composition according to claim 5 , wherein said autoantigen is secreted by an autoantigen secreting Lactococcus lactis.
8. The composition according to claim 5 , wherein said composition is present in a spray, capsule, aerosol, lozenge, bolus, tablet, sachet, liquid, suspension, emulsion, or troche.
9. The composition according to claim 5 , wherein said composition is present in a unit dosage form.
10. The composition according to claim 5 , wherein said composition is a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
11. A method for inducing immune tolerance to type I diabetes in a subject in need thereof comprising mucosally administering to said subject an effective amount of a composition comprising a beta cell autoantigen in type I diabetes and an IL-10 secreting Lactococcus lactic.
12. The method according to claim 11 , wherein said autoantigen is pro-insulin, insulin, an immuno-dominant peptide of insulin or pro-insulin, or a combination thereof.
13. The method according to claim 11 , wherein said autoantigen is secreted by an autoantigen secreting Lactococcus lactic.
14. The method according to claim 11 , wherein said composition is administered to said subject daily for at least 1 week.
15. The method according to claim 11 , wherein said subject is selected from the group consisting of a mouse, a rat, a dog, a cat, a cow, a horse, a pig, and a human.
16. A method for treating type I diabetes in a subject in need thereof, comprising mucosally administering to said subject an effective amount of a composition comprising a beta cell autoantigen in type I diabetes and an IL-10 secreting Lactococcus lactis.
17. The method according to claim 16 , wherein said autoantigen is pro-insulin, insulin, an immuno-dominant peptide of insulin or proinsulin, or a combination thereof.
18. The method according to claim 16 , wherein said autoantigen is secreted by an autoantigen secreting Lactococcus lactis.
19. The method according to claim 16 , wherein said composition is administered to said subject daily for at least 1 week.
20. The method according to claim 16 , wherein said subject is selected from the group consisting of a mouse, a rat, a dog, a cat, a cow, a horse, a pig, and a human.
21. The medicament, nutraceutical, or medical food of claim 3 , wherein said IL-10 secreting Lactococcus lactis and said autoantigen secreting Lactococcus lactis are the same microorganism.
22. The medicament, nutraceutical, or medical food of claim 3 , wherein said IL-10 secreting Lactococcus lactis and said autoantigen secreting Lactococcus lactis are different microorganisms.
23. The composition of claim 7 , wherein said IL-10 secreting Lactococcus lactis and said autoantigen secreting Lactococcus lactis are the same microorganism.
24. The composition of claim 7 , wherein said IL-10 secreting Lactococcus lactis and said autoantigen secreting Lactococcus lactis are different microorganisms.
25. The composition of claim 9 , wherein said unit dosage form is selected from the group consisting of a tablet, a capsule, a lozenge, a sachet, and a metered aerosol dose.
26. The method of claim 13 , wherein, said IL-10 secreting Lactococcus lactis and said autoantigen secreting Lactococcus lactis are the same microorganism.
27. The method of claim 13 , wherein said IL-10 secreting Lactococcus lactis and said autoantigen secreting Lactococcus lactis are different microorganisms.
28. The method of claim 18 , wherein said IL-10 secreting Lactococcus lactis and said autoantigen secreting Lactococcus lactis are the same microorganism.
29. The method of claim 18 , wherein said IL-10 secreting Lactococcus lactis , and said autoantigen secreting Lactococcus lactis are different microorganisms.
30. The method of claim 15 , wherein said subject is a human.
31. The method of claim 20 , wherein said subject is a human.
32. The composition of claim 5 , wherein said autoantigen is a human autoantigen.
33. The composition of claim 32 , wherein said human autoantigen is selected from the group consisting of human proinsulin II B24-C36 peptide (hpllp), human insulin, and human immuno-dominant peptide InsB 9-23 .
34. The method of claim 11 , wherein said autoantigen is a human autoantigen.
35. The method of claim 34 , wherein said human autoantigen is selected from the group consisting of human proinsulin II B24-C36 peptide (hpllp), human insulin, and human immuno-dominant peptide InsB 9-23 .
36. The method of claim 16 , wherein said autoantigen is a human autoantigen.
37. The method of claim 36 , wherein said human autoantigen is selected from the group consisting of human proinsulin II B24-C36 peptide (hpllp), human insulin, and human immuno-dominant peptide InsB 9-23 .
38. The composition of claim 7 , wherein said IL-10 or said autoantigen is encoded by a DNA sequence downstream of a lactococcal P1 promoter.
39. The method of claim 13 , wherein said IL-10 or said autoantigen is encoded by a DNA sequence downstream of a lactococcal P1 promoter.
40. The method of claim 18 , wherein said IL-10 or said autoantigen is encoded by a DNA sequence downstream of a lactococcal P1 promoter.
41. The composition of claim 7 , wherein said IL-10 or said autoantigen is fused to a Usp45 secretion signal.
42. The method of claim 13 , wherein said IL-10 or said autoantigen is fused to a Usp45 secretion signal.
43. The method of claim 18 , wherein said IL-10 or said autoantigen is fused to a Usp45 secretion signal.