Treatment of immune disease by mucosal delivery of antigents using genetically modified
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 method of treating celiac disease in a subject comprising mucosally delivering a composition to the subject, wherein the composition comprises a genetically engineered Lactococcus lactis constitutively expressing and secreting an α-gliadin peptide or a hordein peptide, each peptide comprising a HLA-DQ2-specific epitope or a HLA-DQ8-specific epitope, wherein the composition is delivered mucosally to the subject at least once a day.
2. The method of claim 1 , wherein the method results in the induction of regulatory T (Treg) cells.
3. The method of claim 2 , wherein the Treg cells are Foxp3+cells.
4. The method of claim 1 , wherein the epitope is an immune dominant deamidated epitope.
5. The method of claim 1 , wherein the peptide comprises SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, or SEQ ID NO: 8.
6. The method of claim 1 , wherein the composition is delivered orally.
7. The method of claim 6 , wherein the orally delivered Lactococcus lactis composition suppresses gliadin-specific immune responses in the subject.
8. The method of claim 1 , wherein the mucosal delivery of the composition is performed for at least one week.
9. The method of claim 1 , wherein the mucosal delivery of the composition is performed at least once a day.
10. The method of claim 9 , wherein the mucosal delivery of the composition is performed at least twice a day.
11. The method of claim 1 , wherein the Lactococcus lactis is delivered at a dose of at least 10 femtograms to 500 micrograms daily.
12. The method of claim 1 , wherein the composition is delivered as a capsule, tablet, liquid, suspension, emulsion, or troche.
13. The method of claim 1 , wherein the composition is formulated as a medicament, medical food, or a neutraceutical.
14. The method of claim 1 , wherein a single dose of the composition comprises at least ten femtograms of the Lactococcus lactis.
15. The method of claim 1 , wherein the peptide is expressed and secreted for the continuous presence at the intended mucosal site.