Methods and compositions for adaptive immune modulation

Abstract

Certain embodiments are directed to compositions and methods for attenuating allergic responses in a subject.

1 . A method for attenuating type I hypersensitivity in a subject, comprising administering an effective amount of at a composition comprising at least two TLR agonists to a subject susceptible to allergen induced asthma. 
     
     
         2 . The method of  claim 1 , wherein the subject has been exposed to an allergen. 
     
     
         3 . The method of  claim 2 , wherein the allergen is administered in combination with the TLR agonists. 
     
     
         4 . The method of  claim 1 , wherein the TLR agonists are selected from the group consisting of TLR2/1, TLR2/6, TLR3, TLR4, TLR5, TLR9, and TLR7 agonist. 
     
     
         5 . The method of  claim 1 , wherein the composition comprises a TLR9 agonist and a TLR2/6 agonist. 
     
     
         6 . The method of  claim 1 , wherein at least one of the TLR agonists is a TLR2/6 agonist. 
     
     
         7 . The method of  claim 5 , wherein the TLR2/6 agonist is a diacylated lipopolypeptide. 
     
     
         8 . The method of  claim 5 , wherein the TLR2/6 agonist is PAM2CSK4. 
     
     
         9 . The method of  claim 1 , wherein at least one of the TLR agonists is a TLR9 agonist. 
     
     
         10 . The method of  claim 9 , wherein the TLR9 agonists is a TLR9 oligonucleotide agonist. 
     
     
         11 . The method of  claim 10 , wherein the TLR9 oligonucleotide agonist is a type C oligodeoxynucleotide (ODN), such as ODN2395 (5′-tcgtcgttttcggcgcgcgccg-3′ (SEQ ID NO:1) or ODNM362 (5′-tcgtcgtcgttcgaacgacgttgat-3′ (SEQ ID NO:2) or ODN10101 (5′-tcgtcgttttcgcgcgcgccg-3′ (SEQ ID NO:3) or 9 mer (5′-cgcgaagcg-3′ or H-Tel 22 (5′-agggttagggttagggttaggg-3′ (SEQ ID NO:4) or analog thereof. 
     
     
         12 . The method of  claim 10 , wherein the TLR9 oligonucleotide has a phosphorothioate or phosphodiester backbone. 
     
     
         13 . The method of  claim 9 , wherein the TLR9 agonist is a type C oligodeoxynucleotide (ODN). 
     
     
         14 . The method of  claim 1 , wherein the at least two TLR agonist are PAM2CSK4 and a type C oligodeoxynucleotide (CpG-ODN). 
     
     
         15 . The method of  claim 14 , wherein the CpG-ODN is ODNM362. 
     
     
         16 . The method of  claim 14 , wherein the molar ratio of PAM2CSK to CpG-ODN is 4:1. 
     
     
         17 . The method of  claim 1 , further comprising administering an allergen. 
     
     
         18 . The method of  claim 17 , wherein the allergen is administered concurrently with the at least two TLR agonist. 
     
     
         19 . A pharmaceutically acceptable composition comprising a TLR9 oligonucleotide agonist and a TLR2/6 agonist, an anti-inflammatory agent, or one or more pharmaceutical excipients, wherein said composition is sterile and essentially free of pathogenic microbes. 
     
     
         20 - 25 . (canceled)