Materials and methods for modulating immune responses

Abstract

The present invention provides materials and methods for modulating an immune response. In one embodiment, the present invention provides an initial artificial lymph-node homing environment, and a simultaneous, or subsequent, artificial spleen environment leading to the resolution of the activated immune responses. In one specific embodiment, the present invention can be used to prevent and/or treat pathogenic infection, cancer, allergenic reactions, and/or unwanted immune or auto-immune responses.

We claim: 
     
         1 . A method for inducing a protective immune response against a target antigen, autoantigen or allergen, wherein the method comprises administering, to a subject in need of such an immune response, a pro-inflammatory adjuvant and an anti-inflammatory adjuvant, wherein said method further comprises administering the target antigen, autoantigen or allergen. 
     
     
         2 . The method, according to  claim 1 , wherein the pro-inflammatory adjuvant comprises one or more of the following: aluminum hydroxide (Alum), lipopolysaccharides (LPS), cytosine-guanosine (CpG) oligonucleotide (CpG-ODN) sequences, polyinosinic:polycytidylic acid (poly IC), a pro-inflammatory cytokine, a CpG rich oligonucleotide, leukotriene, arachidonic acids, prostaglandins, an arachidonic acid-pathway activator, a cyclo-oxygenase-pathway activator, incomplete Freund's adjuvant, complete Freund's adjuvant, and Freund's adjuvant with muramyldipeptide (MDP). 
     
     
         3 . The method, according to  claim 1 , wherein the anti-inflammatory adjuvant comprises one or more of the following: hemoglobin:haptoglobin, hemin, heme:hemopexin, a nonsteroidal anti-inflammatory drug (NSAID), a triterpinoid, ethyl pyruvate (EP), a hemeoxygenase (HO-1)-pathway activator, an arachidonic acid-pathway inhibitor, and a COX-pathway inhibitor. 
     
     
         4 . The method, according to  claim 1 , wherein the anti-inflammatory adjuvant is administered after the pro-inflammatory adjuvant. 
     
     
         5 . The method, according to  claim 1 , wherein the pro-inflammatory adjuvant and the anti-inflammatory adjuvant are administered simultaneously. 
     
     
         6 . The method, according to  claim 1 , further comprising administering an immuno-modulating molecule that induces the migration of an immune cell. 
     
     
         7 . The method, according to  claim 6 , wherein the immuno-modulating molecule is selected from GM-CSF, G-CSF, or both. 
     
     
         8 . The method, according to  claim 1 , used to prevent or treat pathogenic infection, cancer, allergy, immune disease, and/or autoimmune disease. 
     
     
         9 . The method, according to  claim 1 , used to prevent or treat type 1 diabetes. 
     
     
         10 . A device for modulating an immune response in a subject, wherein said device comprises: a scaffold matrix made of biocompatible material, wherein the scaffold matrix comprises a pro-inflammatory agent, an anti-inflammatory agent, and an antigen, autoantigen, or allergen. 
     
     
         11 . The device, according to  claim 10 , wherein the scaffold matrix comprises a hydrogel. 
     
     
         12 . The device, according to  claim 10 , wherein the scaffold matrix further comprises an immuno-modulating molecule that induces the migration of an immune cell. 
     
     
         13 . The device, according to  claim 12 , wherein the immuno-modulating molecule is selected from GM-CSF, G-CSF, or both. 
     
     
         14 . The device according to  claim 12 , wherein the scaffold matrix further comprises a microparticle, wherein the microparticle encapsulates therein, at least: said antigen, autoantigen, or allergen, wherein the outer surface of the microparticle comprises one or more surface ligands that bind to the target immune cell. 
     
     
         15 . The device, according to  claim 14 , wherein the microparticle is made of materials comprising PLGA. 
     
     
         16 . A device for modulating an immune response in a subject, wherein said device comprises:
 1) a pro-inflammatory composition comprising: a scaffold matrix comprising:   a) an immuno-modulating molecule that induces the migration of an immune cell,   b) a pro-inflammatory agent, and   c) a microparticle encapsulating therein, at least, an antigen, autoantigen, or allergen; and   2) an anti-inflammatory composition comprising a scaffold matrix, wherein the scaffold matrix comprises an anti-inflammatory agent;   wherein the outer surface of the microparticle comprises one or more surface ligands that bind to the target immune cell.   
     
     
         17 . The device, according to  claim 16 , wherein the anti-inflammatory composition is released after the pro-inflammatory composition is released. 
     
     
         18 . The device, according to  claim 16 , wherein the scaffold matrix is made of materials comprising hydrogel. 
     
     
         19 . The device, according to  claim 16 , wherein the immuno-modulating molecule is selected from GM-CSF, G-CSF, or both. 
     
     
         20 . The device, according to  claim 16 , wherein the immune cell is a dendritic cell.