Adjuvants and methods of use
View Patent ↗Compositions comprising NKT cell agonist compounds and a physiologically acceptable vehicle are provided. Methods of stimulating an NKT cell and enhancing an immune response are also disclosed. Further provided are vaccine preparations comprising NKT cell agonist compounds.
1. A method of enhancing an immune response in a subject comprising administering to the subject a composition comprising a compound of formula (I)
wherein:
X is — 0 —;
R l is —OH;
R 2 is —H;
R 3 is a saturated or unsaturated hydrocarbon group having from about 7 to about 25 carbon atoms;
R 5 is a saturated or unsaturated hydrocarbon group having from about 5 to about 15 carbon atoms,
R 6 together with R 4 forms a carbon-carbon double bond;
R 7 is —OH; and
R 8 is —OSO 3 H, —SO 3 H, —PO 4 , —PO 4 H, or —COOH;
and a physiologically acceptable vehicle.
2. The method of claim 1 , wherein the immune response comprises the production of antibodies or comprises a helper, cytolytic or memory response.
3. The method of claim 1 , wherein R 8 is —OSO 3 H.
4. The method of claim 3 , wherein R 3 is C 25 H 51 and R 5 is C 13 H 27 .
5. The method of claim 1 , wherein R 3 is C 25 H 51 and R 5 is C 13 H 27 .
6. The method of claim 1 , wherein the composition comprises an antigen.
7. The method of claim 6 , wherein the composition is a vaccine.
8. The method of claim 6 , wherein the antigen is a tumor antigen.
9. The method of claim 6 , wherein the antigen is a bacterial or viral antigen.
10. A method of stimulating an NKT cell comprising contacting the NKT cell with a composition comprising a compound having a structural formula represented by (I):
wherein:
X is —O—;
R 1 is —OH;
R 2 , is —H;
R 3 is a saturated or unsaturated hydrocarbon group having from about 7 to about 25 carbon atoms;
R 5 is a saturated or unsaturated hydrocarbon group having from about 5 to about 15 carbon atoms,
R 6 together with R 4 forms a C—C double bond; and
R 7 is —OH; and
R 8 is —OSO 3 H, —SO 3 H, —PO 4 , —PO 4 H, or —COOH.
11. The method of claim 10 , further comprising contacting the NKT cell with the composition in the presence of a CD 1 d monomer or tetramer.
12. The method of claim 11 , wherein the compound is bound to the CD1d monomer or tetramer.
13. The method of claim 11 , wherein the CD1d monomer or tetramer is soluble.
14. The method of claim 11 , wherein the CD1d monomer is expressed on a cell surface.
15. The method of claim 14 , wherein the cell is an antigen presenting cell.
16. The method of claim 10 , wherein the NKT cell is cultured in vitro.
17. The method of claim 10 , wherein the NKT cell is in a subject.
18. The method of claim 10 , wherein R 8 is —OSO 3 H.
19. The method of claim 18 , wherein R 3 is C 25 H 51 and R 5 is C l3 H 27 .
20. The method of claim 10 , wherein R 3 is C 25 H 51 and R 5 is C 13 H 27 .
21. The method of claim 10 , wherein the composition comprises an antigen.
22. The method of claim 21 , wherein the composition is a vaccine.
23. The method of claim 21 , wherein the antigen is a tumor antigen.
24. The method of claim 21 , wherein the antigen is a bacterial or viral antigen.