Immunomodulatory formulations and methods for use thereof

Abstract

The invention provides new compositions and methods for immunomodulation of individuals. Immunomodulation is accomplished by administration of immunomodulatory polynucleotide/microcarrier (IMP/MC) complexes. The IMP/MC complexes may be covalently or non-covalently bound, and feature a polynucleotide comprising at least one immunostimulatory sequence bound to a nonbiodegradable microcarrier or nanocarrier.

1 - 29 . (canceled)  
     
     
         30 . A method of modulating an immune response in an individual comprising administering to an individual a composition comprising an immunomodulatory polynucleotide/microcarrier (IMP/MC) complex in an amount sufficient to modulate an immune response in said individual, said complex comprising a polynucleotide linked to a nonbiodegradable microcarrier (MC), wherein the polynucleotide comprises the sequence 5′-C, G-3′.  
     
     
         31 . The method of  claim 30 , wherein said microcarrier is a solid phase microcarrier.  
     
     
         32 . The method of  claim 30 , wherein said microcarrier is a liquid phase microcarrier.  
     
     
         33 . The method of  claim 30 , wherein said polynucleotide is covalently linked to said microcarrier.  
     
     
         34 . The method of  claim 30 , wherein said polynucleotide is non-covalently linked to said microcarrier.  
     
     
         35 . The method of  claim 30 , wherein said microcarrier is less than about 10 μm in size.  
     
     
         36 . The method of  claim 30 , wherein said complex is antigen-free.  
     
     
         37 . The method of  claim 30 , wherein a Th1-type immune response is stimulated.  
     
     
         38 . The method of  claim 30 , wherein a Th2-type immune response is suppressed.  
     
     
         39 . The method of  claim 30 , wherein interferon-gamma (IFN-γ) is increased in said individual.  
     
     
         40 . The method of  claim 39 , wherein said individual has idiopathic pulmonary fibrosis.  
     
     
         41 . The method of  claim 30 , wherein interferon-alpha (IFN-α) is increased in said individual.  
     
     
         42 . The method of  claim 41 , wherein said individual has a viral infection.  
     
     
         43 . The method of  claim 30 , wherein levels of IgE is reduced in said individual.  
     
     
         44 . The method of  claim 30 , wherein the polynucleotide comprises the sequence 5′-T, C, G-3′.  
     
     
         45 . The method of  claim 30 , wherein the polynucleotide comprises the sequence 5′-purine, purine, C, G, pyrimidine, pyrimidine, C, G-3′.  
     
     
         46 . The method of  claim 44 , wherein the polynucleotide comprises the sequence SEQ ID NO:1.  
     
     
         47 . The method of  claim 44 , wherein the polynucleotide comprises the sequence 5′-TCGX 1 X 2 X 3 X 4 -3′ or the sequence 5′-X 1 TCGX 2 X 3 X 4 -3′, wherein X 1 , X 2 , X 3 , X 4  are nucleotides.  
     
     
         48 . The method of  claim 47 , wherein the polynucleotide comprises the sequence 5′-TCGTCGX 1 -3′, wherein X 1  is a nucleotide.  
     
     
         49 . The method of  claim 47 , wherein the polynucleotide comprises a sequence selected from the group consisting of 5′-TCGTCGA-3′, 5′-TCGAAAA-3′, 5′-TCGCCCC-3′, 5′-TCGGGGG-3′ and 5′-TCGTTTT-3′.  
     
     
         50 . The method of  claim 30 , wherein said polynucleotide further comprises the sequence 5′-T, C, G-3′.  
     
     
         51 . The method of any of claims  30 ,  44 ,  47 ,  48 ,  49  or  50 , wherein said polynucleotide is 7 nucleotides in length.  
     
     
         52 . The method of any of claims  30 ,  44 ,  47 ,  48 ,  49  or  50 , wherein said composition further comprises an antigen.  
     
     
         53 . The method of  claim 52 , wherein said antigen is an allergen.  
     
     
         54 . The method of  claim 30 , wherein said polynucleotide comprises a phosphate backbone modification.  
     
     
         55 . The method of  claim 54 , wherein said phosphate backbone modification is a phosphorothioate.  
     
     
         56 - 79 . (canceled)