TREATMENT OF IMMUNE DISEASE BY MUCOSAL DELIVERY OF ANTIGENTS USING GENETICALLY MODIFIED LACTOBACILLUS
The present invention relates to the treatment of autoimmune and allergic diseases by mucosal delivery by micro-organism, in particular Lactococcus lactis , of secreted immunodominant antigens.
1 . A micro-organism secreting an antigen for use in mucosal delivery to treat an immune response related disease in a patient, wherein said immune response related disease is chosen from the group consisting of allergic asthma, multiple sclerosis, type I diabetes, autoimmune uveitis, autoimmune thyroiditis, autoimmune myasthenia gravis, rheumatoid arthritis, food allergy or celiac disease.
2 . A composition for use in mucosal delivery to treat, prevent and/or alleviate an immune response related disease chosen from the group consisting of allergic asthma, multiple sclerosis, type I diabetes, autoimmune uveitis, autoimmune thyroiditis, autoimmune myasthenia gravis, rheumatoid arthritis, food allergy or celiac disease in a patient, characterized in that said composition comprises at least a micro-organism secreting an antigen.
3 . The composition of claim 2 , wherein said micro-organism is lactic acid bacterium, yeast, or Lactococcus lactis (LL).
4 . The composition of claim 2 , wherein said antigen is constitutively secreted.
5 . The composition of claim 2 , wherein said micro-organism is administered daily.
6 . The composition of claim 2 , wherein said antigen induces regulatory T-cells (Treg).
7 . The composition according to claim 6 , wherein said Treg cells are Foxp3+ Treg cells.
8 . The composition of claim 7 , wherein said antigen is an immuno-dominant deamidated antigen.
9 . The composition of claim 8 , wherein said antigen is recognized in the context of HLA-DQ2 or -DQ8.
10 . The composition of claim 9 , wherein said antigen is α-gliadin or hordein.
11 . The composition for use according to claim 10 , wherein said antigen comprises or consists of SEQ ID NO: 2, 4, 6 or 8.
12 . The composition of claim 2 , wherein said antigen reduces proliferation of spleen and inguinal lymph node cells.
13 . The composition or claim 2 , wherein said antigen suppresses inflammatory antigen specific T cell response.
14 . The composition of claim 2 , 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.
15 . The composition of claim 2 , wherein said micro-organism is delivered for at least 1 week, 1 month or 1 year.
16 . The composition of claim 2 , wherein said micro-organism is delivered at least once or twice a day.
17 . The composition of claim 2 , wherein said micro-organism is delivered in a dose of at least 10 femtogram to 100 mg per day.
18 . The composition of claim 2 , wherein said micro-organism is delivered by spray, capsule, aerosol, lozenges, bolus, tablet, sachets, liquid, suspension, emulsion or troches.
19 . The composition of claim 2 , wherein said composition is formulated as a medicament, medical food or nutraceutical.
20 . Method for treating, preventing and/or alleviating an immune response related disease in a patient, comprising the mucosal delivery of a composition comprising a micro-organism expressing an antigen, wherein said antigen is secreted, and wherein said composition is delivered daily.
21 . The method according to claim 20 , wherein said micro-organism is lactic acid bacterium, yeast or Lactococcus lactis (LL).
22 . The method according to claim 20 , wherein disease is selected from the group consisting of allergic asthma, multiple sclerosis, type I diabetes, autoimmune uveitis, autoimmune thyroiditis, autoimmune myasthenia gravis, rheumatoid arthritis, food allergy and celiac disease.
23 . The method according to claim 20 , wherein said secretion is constitutive.
24 . The method according to claim 20 , wherein said antigen induces regulatory T-cells (Treg).
25 . The method according to claim 24 , wherein said Treg cells are Foxp3+ Treg cells.
26 . The method according to claim 20 , wherein said antigen is an immuno dominant deamidated antigen.
27 . The method according to claim 20 , wherein said antigen is recognized in the context of HLA-DQ2 or -DQ8.
28 . The method according to claim 20 , wherein said antigen is α-gliadin or hordein.
29 . The method according to claim 28 , wherein said antigen comprises or consists of SEQ ID NO: 2, 4, 6 or 8.
30 . The method according to claim 20 , wherein said antigen reduces proliferation of spleen and inguinal lymph node cells.
31 . The method according to claim 20 , wherein said antigen suppresses inflammatory antigen specific T cell response.
32 . The method according to claim 20 , wherein said mucosal delivery is chosen from the group consisting of rectal delivery, buccal delivery, pulmonary delivery, ocular delivery, nasal delivery, vaginal delivery and oral delivery.
33 . The method according to claim 20 , wherein said micro-organism is delivered for at least 1 week, 1 month or 1 year.
34 . The method according to claim 20 , wherein said micro-organism is delivered at least once or twice a day.
35 . The method according to claim 20 , wherein said micro-organism is delivered in a dose of at least 10 femtogram to 100 mg per day.
36 . The method according to claim 20 , wherein said micro-organism is delivered by spray, capsule, aerosol, lozenges, bolus, tablet, sachets, liquid, suspension, emulsion or troches.
37 . Composition comprising a micro-organism, wherein said micro-organism constitutively secretes an antigen, which is involved in the induction of allergic asthma, multiple sclerosis, type I diabetes, autoimmune uveitis, autoimmune thyroiditis, autoimmune myasthenia gravis, rheumatoid arthritis, food allergy or celiac disease.
38 . The composition according to claim 37 , wherein said micro-organism is lactic acid bacterium or yeast or Lactococcus lactis (LL).
39 . The composition of claim 37 , wherein said micro-organism is present in a dose of at least 10 femtogram to 100 mg, such as 100 fg to 10 mg, or 1 pg to 1 mg, or 10 pg to 100 μg, or 100 pg to 10 μg, or 1 ng to 1 μg, or 10 ng to 100 mg.
40 . Product comprising the composition of claim 37 .
41 . The product of claim 40 , wherein said product is selected from the group consisting of sprays, capsules, aerosols, lozenges, bolus, tablets, sachets, liquids, suspensions, emulsions and troches.
42 . Medicament, nutraceutical or medical food for treating, preventing and/or alleviating a disease or disorder involving an immune response related disease comprising at least a micro organism, wherein said micro-organism constitutively secretes an antigen, which is involved in the induction of allergic asthma, multiple sclerosis, type I diabetes, autoimmune uveitis, autoimmune thyroiditis, autoimmune myasthenia gravis, rheumatoid arthritis, food allergy or celiac disease.
43 . Medicament, nutraceutical or medical food according to claim 42 , wherein said micro organism is lactic acid bacterium or yeast or Lactococcus lactis (LL).
44 . The composition of claim 2 , wherein said antigen is prepared for the continued presence in said patient.