Method for Inducing a TRIF-Bias

Abstract

Compositions comprising a selected aminoalkyl glusoaminide 4-phosphate (AGP) CRX-547 to induce a TRIF-biased response in a human system, which results in reduced levels of MyD88-dependent cytokines relative to the MyD88-dependent cytokines induced by its diastereomer AGP CRX-527.

1 . A lipid A mimetic composition with an improved therapeutic index comprising:
 a first and a second aminoalkyl glucosaminide phosphate (AGP)   wherein the first AGP is not CRX 547 and   wherein the second AGP is CRX 547 and   wherein the therapeutic index of the composition is improved by substantially maintaining or increasing a TRIF-dependent cytokine reponse and by lowering a MyD88-dependent cytokine response relative to the TRIF-dependent cytokine reponse and MyD88-dependent cytokine response of the composition in the absence of CRX 547.   
     
     
         2 . The composition of  claim 1  wherein the composition's MyD88-dependent cytokine response induces less inflammation when said composition is administered to a subject, relative to the inflammation induced by the composition in the absence of CRX 547. 
     
     
         3 . The composition of  claim 1  wherein the composition's TRIF-dependent cytokine response induces an effective immune response when said composition is administered to a subject, relative to the immune response induced by the composition in the absence of CRX 547. 
     
     
         4 . The composition of  claim 1  wherein the first AGP is CRX 527.