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 composition comprising:
(a) a Lactococcus lactis secreting interleukin 10 (IL-10), and
(b) a Lactococcus lactis expressing an allergen.
2. The composition according to claim 1 , wherein said composition further comprises a pharmaceutically acceptable carrier and/or excipient.
3. The composition according to claim 1 , wherein said allergen is displayed at the surface of said Lactococcus lactis expressing said allergen.
4. The composition according to claim 1 , wherein said allergen is secreted by said Lactococcus lactis expressing said allergen.
5. The composition according to claim 1 , wherein said Lactococcus lactis expressing said allergen and said Lactococcus lactis secreting IL-10 are present in a spray, a capsule, an aerosol, a lozenge, a bolus, a tablet, a sachet, a liquid, a suspension, an emulsion, or a troche.
6. The composition according to claim 1 , wherein said Lactococcus lactis expressing said allergen and said Lactococcus lactis secreting IL-10 are present in a unit dosage form selected from the group consisting of a tablet, a capsule, and a metered aerosol dose.
7. The composition according to claim 1 , wherein said allergen and said IL-10 are expressed by the same Lactococcus lactis.
8. The composition according to claim 1 , further comprising an adjuvant.
9. The composition according to claim 1 , further comprising a compound stimulating production of IL-10.
10. The composition according to claim 9 , wherein said compound stimulating production of IL-10 is cholera toxin B subunit.
11. The composition according to claim 1 , wherein said Lactococcus lactis secreting IL-10 is present in a dose of at least 10 femtogram to 100 mg.
12. The composition according to claim 1 , further comprising an anti-CD3 antibody.
13. The composition according to claim 1 , wherein said allergen is involved in an allergic reaction, an allergic asthma, or a food allergy.
14. A method to induce tolerance to an allergen in a mammal comprising administering to a mammal in need thereof by mucosal delivery in an amount effective to induce tolerance to said allergen:
(a) a Lactococcus lactis secreting interleukin 10 (IL-10), and
(b) a Lactococcus lactis expressing said allergen.
15. The method according to claim 14 , wherein said mammal is selected from the group consisting of mouse, rat, dog, cat, cattle, horse, pig, and human.
16. The method according to claim 14 , further comprising administering to said mammal an anti-CD3 antibody.
17. The method according to claim 14 , wherein said allergen is displayed at the surface of said Lactococcus lactis expressing said allergen.
18. The method according to claim 14 , wherein said allergen is secreted by said Lactococcus lactis expressing said allergen.
19. The method according to claim 14 , 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.
20. The method according to claim 14 , wherein said Lactococcus lactis expressing said allergen and/or said Lactococcus lactis secreting IL-10 are delivered by a spray, a capsule, an aerosol, a lozenge, a bolus, a tablet, a sachet, a liquid, a suspension, an emulsion, or a troche.
21. The method according to claim 14 , wherein said Lactococcus lactis expressing said allergen and said Lactococcus lactis secreting IL-10 are delivered in a unit dosage form selected from the group consisting of a tablet, a capsule, and a metered aerosol dose.
22. The method according to claim 14 , wherein said Lactococcus lactis expressing said allergen is delivered simultaneously with or sequential to said Lactococcus lactis secreting IL-10.
23. The method according to claim 14 , wherein said allergen and said IL-10 are expressed by the same Lactococcus lactis.
24. The method according to claim 14 , wherein said Lactococcus lactis expressing said allergen and/or said Lactococcus lactis secreting IL-10 is contained in a composition comprising an adjuvant, a pharmaceutically acceptable carrier, and/or an excipient.
25. The method according to claim 14 , wherein said Lactococcus lactis expressing said allergen and/or said Lactococcus lactis secreting IL-10 is contained in a composition comprising a compound stimulating production of immunosuppressing cytokines.
26. The method according to claim 25 , wherein said compound is cholera toxin B subunit.
27. The method according to claim 14 , wherein said Lactococcus lactis secreting IL-10 is administered to said mammal for at least 5 days.
28. The method according to claim 14 , wherein said Lactococcus lactis expressing said allergen and said Lactococcus lactis secreting IL-10 are administered to said mammal at least once a day.
29. The method according to claim 14 , wherein said Lactococcus lactis expressing said allergen and said Lactococcus lactis secreting IL-10 are delivered in a dose of 10 femtogram to 100 mg per day.
30. The method according to claim 14 , wherein said allergen is involved in an allergic reaction, an allergic asthma, or a food allergy.