Immunization-free methods for treating antigen-stimulated inflammation in a mammalian host and shifting the host's antigen immune responsiveness to a th1 phenotype

Abstract

The invention relates to methods for preventing or reducing antigen-stimulated, granulocytemediated inflammation in tissue of an antigen-sensitized mammal host by delivering an immunostimulatory oligonucleotide to the host. In addition, methods for using the immunostimulatory oligonucleotides to boost a mammal host's immune responsiveness to a sensitizing antigen (without immunization of the host by the antigen) and shifting the host's immune responsiveness to a Th1 phenotype to achieve various therapeutic ends are provided. Kits for practicing the methods of the invention are also provided.

1 .- 37 . (canceled) 
     
     
         38 . A method for treating antigen-stimulated inflammation in a mammal, comprising: administering to a mammal sensitized to an antigen an immunostimulatory polynucleotide comprising an immunostimulatory sequence (ISS), wherein the ISS comprises the sequence 5′-cytosine-guanine-3′, wherein the ISS is from about 6 to about 200 nucleotides in length, wherein the immunostimulatory polynucleotide does not comprise a nucleotide sequence encoding the antigen, and wherein the immunostimulatory polynucleotide is administered without the antigen, including without a polynucleotide encoding the antigen, and in an amount sufficient to treat the antigen-stimulated inflammation. 
     
     
         39 . The method of  claim 38 , wherein the ISS comprises the sequence 5′-purine-purine-cytosine-guanine-pyrimidine-pyrimidine-3′. 
     
     
         40 . The method of  claim 39 , wherein the ISS comprises a nucleotide sequence selected from AGCGTC, GACGTT, GGCGTT, AACGTC, GACGTC, GGCGTC, AGCGCC, GACGCC, GGCGCC, AGCGCT, GACGCT, GGCGCT, AACGCT, AACGTT, AGCGTT, and AACGCC. 
     
     
         41 . The method of  claim 38 , wherein the mammal is a human. 
     
     
         42 . The method of  claim 38 , wherein the immunostimulatory polynucleotide is administered intramuscularly. 
     
     
         43 . The method of  claim 38 , wherein the immunostimulatory polynucleotide is administered to skin. 
     
     
         44 . The method of  claim 38 , wherein the immunostimulatory polynucleotide is administered to mucosal tissue. 
     
     
         45 . The method of  claim 44 , wherein the mucosal tissue is respiratory tissue. 
     
     
         46 . The method of  claim 45 , wherein said administration is intranasal. 
     
     
         47 . The method of  claim 38 , wherein the antigen-stimulated inflammation is an allergic condition. 
     
     
         48 . The method of  claim 38 , wherein IgE production in response to the sensitizing antigen is reduced. 
     
     
         49 . The method of  claim 38 , wherein the antigen-stimulated inflammation is Th2 associated inflammation. 
     
     
         50 . A method for treating antigen-stimulated inflammation in a mammal, comprising: administering to a mammal sensitized to an antigen an immunostimulatory polynucleotide comprising an immunostimulatory sequence (ISS), wherein the ISS comprises the sequence 5′-purine-purine-cytosine-guanine-pyrimidine-pyrimidine-3′, wherein the immunostimulatory polynucleotide does not comprise a nucleotide sequence encoding the antigen, and wherein the immunostimulatory polynucleotide is administered without the antigen, including without a polynucleotide encoding the antigen, and in an amount sufficient to treat the antigen-stimulated inflammation. 
     
     
         51 . The method of  claim 50 , wherein the mammal is a human. 
     
     
         52 . The method of  claim 50 , wherein the immunostimulatory polynucleotide is administered intramuscularly. 
     
     
         53 . The method of  claim 50 , wherein the immunostimulatory polynucleotide is administered to skin. 
     
     
         54 . The method of  claim 50 , wherein the immunostimulatory polynucleotide is administered to mucosal tissue. 
     
     
         55 . The method of  claim 54 , wherein the mucosal tissue is respiratory tissue. 
     
     
         56 . The method of  claim 55 , wherein said administration is intranasal. 
     
     
         57 . The method of  claim 50 , wherein the antigen-stimulated inflammation is an allergic condition. 
     
     
         58 . The method of  claim 50 , wherein IgE production in response to the sensitizing antigen is reduced. 
     
     
         59 . The method of  claim 50 , wherein the antigen-stimulated inflammation is Th2 associated inflammation. 
     
     
         60 . The method of  claim 50 , wherein the ISS is from about 6 to about 200 nucleotides in length. 
     
     
         61 . A method of shifting an immune response to an antigen away from a Th2 phenotype and toward a Th1 phenotype in a mammal, the method comprising administering to a mammal sensitized to an antigen an immunostimulatory polynucleotide comprising an immunostimulatory sequence (ISS), wherein the ISS comprises the sequence 5′-cytosine-guanine-3′, wherein the ISS is from about 6 to about 200 nucleotides in length, wherein the immunostimulatory polynucleotide does not comprise a nucleotide sequence encoding the antigen, and wherein the immunostimulatory polynucleotide is administered without the antigen, including without a polynucleotide encoding the antigen, and in an amount sufficient to shift the immune response toward a Th1 phenotype.