Synthetic derivatives of MPL and uses thereof
In one aspect, the present disclosure provides compounds of formulae I and II. In another aspect, a compound of formula I or II is formulated into compositions with an antigen, optionally with a vesicle. In some embodiments, compositions are administered intramuscularly.
1. A composition comprising:
(i) a non-ionic surfactant vesicle comprising: 1-monopalmitoyl glycerol, dicetyl phosphate, and cholesterol; and an immunostimulatory amount of a compound of formula I which is co-melted with the non-ionic surfactant vesicle,
wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are C x alkyl; x is an integer from 6 to 11; and
R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are the same; and
(ii) an antigen.
2. The composition of claim 1 , wherein x is 6.
3. The composition of claim 1 , wherein x is 8.
4. The composition of claim 1 , wherein x is 11.
5. The composition of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are unbranched.
6. The composition of claim 1 , wherein the antigen is a virus selected from the group consisting of an attenuated virus, an inactivated virus, a whole virus and a split virus.
7. The composition of claim 6 , wherein the virus is hepatitis A or influenza.
8. The composition of claim 1 , wherein the antigen is a bacteria selected from the group consisting of Bordetella pertussis, Vibrio cholerae and Salmonella typhi.
9. The composition of claim 1 , wherein the antigen is a polypeptide.
10. The composition of claim 9 , wherein the polypeptide is a viral polypeptide.
11. The composition of claim 10 , wherein the viral polypeptide is selected from the group consisting of a hepatitis A polypeptide, a hepatitis B polypeptide, HBsAg, a hepatitis C polypeptide, an HIV polypeptide and an influenza polypeptide.
12. The composition of claim 9 , wherein the polypeptide is hemagglutinin, neuraminidase, or a combination thereof.
13. The composition of claim 1 , wherein the composition comprises a mixture of antigens.
14. The composition of claim 1 , wherein the composition comprises a mixture of polypeptides.
15. The composition of claim 1 , wherein the antigen is a polynucleotide.
16. The composition of claim 1 , wherein the antigen is a polysaccharide.
17. The composition of claim 1 , wherein the antigen is a viral-like particle.
18. A method comprising administering to a patient in need thereof a therapeutically effective amount of the composition of claim 1 .
19. The method of claim 18 , wherein the composition is administered by intramuscular injection.