Induction of mucosal tolerance to antigens
Induction of tolerance to antigens by mucosal, preferably oral, delivery of the antigen in combination with an immunomodulating compound producing micro-organism is disclosed. More specifically, Foxp3 + and/or IL-10 and/or TGF-β producing regulatory T-cells are induced which are capable of suppressing undesired immune responses toward an antigen. The antigen is preferably delivered orally in combination with an immunosuppressing cytokine secreting micro-organism.
1. A composition for treating celiac disease comprising an IL-10 secreting Lactococcus lactis in combination with gliadin, or in combination with a gliadin peptide which binds HLA-DQ2 and/or HLA-DQ8.
2. A method for treating celiac disease comprising administering the composition of claim 1 to a mammal in need thereof.
3. The method according to claim 2 , wherein the composition is delivered to the mammal in need thereof by mucosal delivery.
4. The method according to claim 2 , wherein said mammal is selected from the group consisting of mouse, rat, dog, cat, cattle, horse, pig and human.
5. The method according to claim 3 , wherein said gliadin or gliadin peptide provokes a T-cell mediated and/or B-cell mediated immune response.
6. The method according to claim 5 , wherein said T-cell mediated immune response is a Th1 immune response or a Th2 immune response.
7. The method according to claim 2 , wherein said composition further comprises Anti-CD3 antibody.
8. The method according to claim 2 , wherein said gliadin or gliadin peptide is delivered by Lactococcus lactis expressing gliadin or liadin peptide.
9. The method according to claim 8 , wherein said gliadin or gliadin peptide is displayed at the surface of said Lactococcus lactis expressing said gliadin or gliadin peptide.
10. The method according to claim 8 , wherein said gliadin or gliadin peptide is secreted.
11. The method according to claim 3 , wherein said mucosal delivery is selected from the group consisting of rectal delivery, buccal delivery, pulmonary delivery, ocular delivery, nasal delivery, vaginal delivery and oral delivery.
12. The method according to claim 2 , wherein said gliadin or gliadin peptide and/or said IL-10 secreting Lactococcus lactis are delivered by spray, capsule, aerosol, lozenges, bolus, tablet, sachets, liquid, suspension, emulsion or troches.
13. The method according to claim 2 , wherein said gliadin or gliadin peptide and said IL-10 secreting Lactococcus species are delivered in a unit dosage form, selected from a tablet, capsule or metered aerosol dose.
14. The method according to claim 2 , wherein said gliadin or gliadin peptide is delivered simultaneously with or sequential to said IL-10 secreting Lactococcus lactis.
15. The method according to claim 2 , wherein said gliadin or gliadin peptide and said IL-10 are expressed by the same Lactococcus lactis.
16. The method according to claim 2 , wherein said composition further comprises an adjuvant, pharmaceutical acceptable carrier and/or excipient.
17. The method according to claim 2 , wherein said composition further comprises a compound stimulating production of immuno-suppressing cytokines.
18. The method according to claim 17 , wherein said compound stimulating production of IL-10 is cholera toxin B subunit.
19. The method according to claim 2 , wherein said IL-10 secreting Lactococcus lactis is delivered for at least 1 day.
20. The method according to claim 2 , wherein said gliadin or gliadin peptide and said IL-10 secreting Lactococcus lactis are delivered at least once a day.
21. The method according to claim 2 , wherein said gliadin or gliadin peptide and/or said IL-10 secreting Lactococcus lactis is delivered in a dose of 10 femtogram to 100 mg per day.
22. The composition according to claim 1 , wherein said composition is a pharmaceutical composition.
23. The composition according to claim 1 , wherein said gliadin or gliadin peptide is delivered by Lactococcus lactis expressing said gliadin or gliadin peptide.
24. The composition according to claim 23 , wherein said gliadin or gliadin peptide is displayed at the surface of said Lactococcus lactis expressing said gliadin or gliadin peptide.
25. The composition according to claim 24 , wherein said gliadin or gliadin peptide is secreted.
26. The composition according to claim 1 , wherein said gliadin or gliadin peptide and/or said IL-10 expressing Lactococcus lactis are present in a spray, capsule, aerosol, lozenges, bolus, tablet, sachets, liquid, suspension, emulsion or troches.
27. The composition according to claim 1 , wherein said gliadin or gliadin peptide and said IL-10 expressing Lactococcus lactis are present in a unit dosage form, for example a tablet, capsule or metered aerosol dose.
28. The composition according to claim 1 , wherein said gliadin peptide and said IL-10 are expressed by the same Lactococcus lactis.
29. The composition according to claim 1 , further comprising an adjuvant, pharmaceutical acceptable carrier and/or excipient.
30. The composition according to claim 1 , further comprising a compound stimulating production of IL-10.
31. The composition according to claim 30 , wherein said compound stimulating production of IL-10 is cholera toxin B subunit.
32. The composition according to claim 1 , wherein said IL-10 secreting Lactococcus lactis are present in a dose of at least at least 10 femtogram to 100 mg.
33. The composition according to claim 1 , further comprising anti-CD3 antibody.