Conjugates of synthetic TLR agonists and uses therefor
The invention provides TLR agonists and conjugates thereof useful in vaccines and to prevent, inhibit or treat a variety of disorders including pathogen infection and asthma.
1. A method for inducing an immune response in a mammal comprising: administering to a mammal a compound of formula A in an amount effective to induce an immune response in the mammal, the compound of formula A having the structure:
or a pharmaceutically acceptable salt thereof, wherein:
X 1 is —O—;
R 1 is hydrogen, (C 1 -C 10 )alkyl or (C 1 -C 10 )alkyl substituted with (C 1 -C 6 )alkoxy;
X 2 is C(O); and
R 3 is dioleoylphosphatidyl ethanolamine (DOPE).
2. The method of claim 1 , wherein R 1 of the compound of Formula A is a (C 1 -C 10 )alkyl substituted with (C 1 -C 6 )alkoxy.
3. The method of claim 1 , wherein R 1 of the compound of Formula A is —(CH 2 ) 2 —OCH 3 .
4. The method of claim 1 , wherein the compound of Formula A is a compound of formula
5. The method of claim 1 , further comprising administering to the mammal an antigen.
6. The method of claim 5 , wherein the antigen is the antigen of a microbe, the antigen of a virus or a cancer antigen.
7. The method of claim 5 , wherein the antigen comprises the antigen of a microbe.
8. The method of claim 7 , wherein the microbe is a bacteria.
9. The method of claim 8 , wherein the bacteria is gram-positive.
10. The method of claim 9 , wherein the gram-positive bacteria is Staphylococcus aureus.
11. The method of claim 9 , wherein the gram-positive bacteria is Bacillus anthracis.
12. The method of claim 7 , wherein the antigen of a microbe is spores of a gram-positive bacterium.