Immunostimulatory combinations of tlr ligands and methods of use

Abstract

The present invention provides immunostimulatory combinations of TLR ligands and therapeutic and/or prophylactic methods that include administering an immunostimulatory combination to a subject. In general, the immunostimulatory combinations described herein can provide an increased immune response compared to other immunostimulatory combinations and/or compositions.

1 - 78 . (canceled) 
     
     
         79 . An immunostimulatory composition for inducing high functional avidity T cells comprising an effective amount of a triple combination of TLR agonists which synergistically activate IL-15 and IL-12 production of dendritic cells as compared to a double combination of TLR agonists thereby inducing high functional avidity T cells. 
     
     
         80 . The immunostimulatory composition of  claim 79 , wherein the triple combination of TLR agonists comprises a TLR2, TLR3, and TLR9 agonist. 
     
     
         81 . The immunostimulatory composition of  claim 80 , wherein the TLR2 agonist is MALP-2, the TLR3 agonist is polyl:C, and the TLR9 agonist is CpG. 
     
     
         82 . The immunostimulatory composition of  claim 79  further comprising one or more antigens. 
     
     
         83 . The immunostimulatory composition of  claim 82  wherein the antigen is conjugated to a TLR agonist. 
     
     
         84 . An immunostimulatory composition according to  claim 79  that is effective for inducing an immune response to the antigen in a subject immunized with the immunostimulatory composition. 
     
     
         85 . The immunostimulatory composition according to  claim 79  wherein the antigen comprises a tumor antigen, a viral antigen, a bacterial antigen, a fungal antigen, a parasitic antigen, an alloantigen, or a xenoantigen. 
     
     
         86 . A method of activating dendritic cells (DCs) to form high functional avidity T cells in a subject comprising administering to the subject an effective amount of a immunostimulatory composition comprising an effective amount of a triple combination of TLR agonists which synergistically activates IL-15 and IL-12 production of the dendritic cells as compared to a double combination of TLR agonists thereby inducing high functional avidity T cells. 
     
     
         87 . The method of  claim 86 , wherein the triple combination of TLR agonists comprises a TLR2, TLR3, and TLR9 agonist. 
     
     
         88 . The method of  claim 86 , wherein the TLR2 agonist is MALP-2, the TLR3 agonist is polyl:C, and the TLR9 agonist is CpG. 
     
     
         89 . The method of  claim 86 , wherein the composition further comprises one or more antigens. 
     
     
         90 . The method of  claim 89 , wherein the one or more antigens are conjugated to a TLR agonist. 
     
     
         91 . The method of  claim 86 , wherein each TLR agonist alone induces limited or no immune response. 
     
     
         92 . The method of  claim 86 , further comprising co-administering one or more antigens. 
     
     
         93 . A method of activating antigen-specific CD8 +  T cells in a subject comprising administering to the subject an effective amount of the immunostimulatory composition of  claim 79 . 
     
     
         94 . A pharmaceutical composition for inducing high functional avidity T cells comprising an effective amount of a triple combination of TLR agonists which synergistically activates IL-15 and IL-12 production of dendritic cells as compared to a double combination of TLR agonists there by inducing high functional avidity T cells. 
     
     
         95 . The pharmaceutical composition of  claim 94 , wherein the triple combination of TLR agonists comprises a TLR2, TLR3, and TLR9 agonist. 
     
     
         96 . The pharmaceutical composition of  claim 95 , wherein the TLR2 agonist is MALP-2, the TLR3 agonist is polyl:C, and the TLR9 agonist is CpG. 
     
     
         97 . The pharmaceutical composition of  claim 94  further comprising one or more antigens. 
     
     
         98 . The pharmaceutical composition of  claim 97  wherein the one or more antigens are conjugated to a TLR agonist.