Immunostimulatory compositions and methods of stimulating an immune response

1. An immunostimulatory composition comprising:

an immune response modifier (IRM) portion of the formula:

 and having IRM activity; and

a portion having antigenic activity that comprises:

an antigenic portion, or

a solid support to which an antigenic moiety is paired;

wherein the immune response modifier portion is covalently coupled to the portion having antigenic activity through R 1 , R 2 , R 3 , or R 4 :

wherein the immune response modifier portion comprises an imidazoquinoline amine; a tetrahydroimidazoquinoline amine; an imidazopyridine amine; an aryl ether-substituted imidazopyridine amine; a 1,2-bridged imidazoquinoline amine; a 6,7-fused cycloalkylimidazopyridine amine; an imidazonaphthyridine amine; a tetrahydroimidazonaphihyndine amine; an oxazoloquinoline amine; a thiazoloquinoline amine; an oxazolopyridine amine; a thiazolopyridine amine; an oxazolonaphthyridine amine; or a thiazolonaphthyridine amine; and

wherein the antigenic portion or antigenic moiety comprises a polypeptide, a polynucleotide, or a lipopolysaccharide.

2. The immunostimulatory composition of claim 1 wherein the immune response modifier portion is an agonist of Toll-like receptor 2, Toll-like receptor 4, Toll-like receptor 6, Toll-like receptor 7, or Toll-like receptor 8.

3. The immunostimulatory composition of claim 1 wherein the polypeptide is a protein.

4. The immunostimulatory composition of claim 1 wherein the immune response modifier portion is a compound of the formula:

wherein:

R 1 is a linker group;

R 2 is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-substituted aryl;

-heteroaryl;

-substituted heteroaryl;

-alkyl-O-alkyl;

-alkyl-S-alkyl;

-alkyl-O-aryl;

-alkyl-S-aryl:

-alkyl-O-alkenyl;

-alkyl-S-alkenyl; and

-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:

—OH;

-halogen;

—N(R 5 ) 2 ;

—CO—N(R 5 ) 2 ;

—CS—N(R 5 ) 2 ;

—SO 2 —N(R 5 ) 2 ;

—NR 5 —CO—C 1-10 alkyl;

—NR 5 —CS—C 1-10 alkyl;

—NR 5 —SO 2 —C 1-10 alkyl;

—CO—C 1-10 alkyl;

—CO—O—C 1-10 alkyl;

—N 3 ;

-aryl;

-substituted aryl;

-heteroaryl;

-substituted heteroaryl;

-heterocyclyl;

-substituted heterocyclyl;

—CO-aryl;

—CO-(substituted aryl);

—CO-heteroaryl; and

—CO-(substituted heteroaryl);

R 3 and R 4 are each independently:

-hydrogen;

-halogen;

-alkyl;

-alkenyl;

—O-alkyl;

—S-alkyl; and

—N(R 5 ) 2 ;

or when taken together, R 3 and R 4 form a fused aryl or heteroaryl group that is optionally substituted by one or more substituents selected from the group consisting of;

-halogen;

-alkyl;

-alkenyl;

—O-alkyl;

—S-alkyl; and

—(R 5 ) 2 ;

or when taken together, R 3 and R 4 form a fused 5 to 7 membered saturated ring, optionally containing one or more heteroatoms and optionally substituted by one or more substituents selected from the group consisting of;

-halogen;

-alkyl;

-alkenyl;

—O-alkyl;

—S-alkyl; and

—N(R 5 ) 2 ; and

each R 5 is independently hydrogen or C 1-10 alkyl.

5. The immunostimalatory composition of claim 1 wherein the immune response modifier portion is covalently coupled to the portion having antigenic activity through R 1 .