Lipidic Compositions for Induction of Immune Tolerance
This invention provides a method for inducing immune tolerance toward an antigen comprising the antigen in lipidic particles or lipidic compositions. The lipidic particles are made up of phosphatidylserine and phosphatidylcholine, or phosphatidylinositol and phosphatidylcholine. The lipidic compositions comprise the antigen and O-phospho-L-serine. Administration of these composition results in inducing immune tolerance to the antigen.
1 . A method for inducing immune tolerance toward an antigen comprising the steps of:
a) preparing lipidic particles comprising the antigen and a phospholipid composition selected from the group consisting of:
i) PC:PI in a ratio of 40:60 to 60:40, and
ii) PS:PC in a ratio of 10:90 to 30:70; and
b) administering the lipidic particles to an individual who has immune intolerance to the antigen,
wherein the administration results in inducing immune tolerance in the individual to the antigen and wherein the antigen is a protein, polypeptide or peptide.
2 . The method of claim 1 , wherein induction of immune tolerance is evidenced by one or more of the following:
i) reduction in antibody titer relative to the titer present prior to administration,
ii) increase in TGF-β and/or IL-10 levels
iii) reduction in one or more of the following: CD40, CD80, CD86, IL-6, IL-17.
3 . The method of claim 1 , wherein the composition of i) further comprises cholesterol such that cholesterol is 1-20% of PC and PI together.
4 . The method of claim 3 , wherein the cholesterol is 5-15% of PC and PI together.
5 . The method of claim 1 , wherein the composition comprising PC and PI further comprises from 100 to 400 mM NaCl.
6 . The method of claim 5 , wherein the composition further comprises from 0.1 to 1.0 mM calcium.
7 . The method of claim 1 , wherein the ratio of PC:PI is 45:55 to 55:45.
8 . The method of claim 1 , wherein the at least 50, 60, 70, 80 or 95% of the particles are from 60 to 140 nm.
9 . The method of claim 1 , wherein the antigen associated with the lipidic particles is present in the ratio of 1:2,000 to 1:4,000.
10 . A method for inducing immune tolerance toward an antigen comprising the steps of:
a) preparing lipidic composition comprising the antigen and OPLS; and
b) administering the lipidic composition from a) to an the individual who has immune intolerance to an antigen,
wherein the administration results in inducing immune tolerance in the individual to the antigen, wherein the antigen is a protein, polypeptide or a peptide.
11 . The method of claim 10 , wherein induction of immune tolerance is evidenced by one or more of the following:
i) reduction in antibody titer relative to the titer present prior to administration,
ii) increase in TGF-β and/or IL-10 levels
iii) reduction in one or more of the following: CD40, CD80, CD86, IL-6, IL-17.
12 . A composition comprising stabilized lipidic nanoparticles comprising an antigen incoporated therein, wherein the phospholipids of the lipidic nanoparticles are selected from the group consisting of PC:PI ratio of 40:60 to 60:40 and wherein the lipid nanoparticles are stabilized by a buffer containing sodium chloride from 100 to 400 mM.
13 . The composition of claim 12 further comprising 0.1 to 1.0 mM calcium.
14 . The composition of claim 13 , wherein the NaCl is from 150 to 300 mM.
15 . The composition of claim 14 , wherein the calcium is from 0.15 to 0.35 mM.