Immunostimulatory nucleic acid molecules

Abstract

Nucleic acids containing unmethylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response and to redirect a Th2 response to a response in a subject are disclosed. Methods for treating atopic diseases, including atopic dermatitis, are disclosed.

1 - 18  (canceled)  
     
     
         19 . A method for effecting an improved response to a vaccine, comprising administering to a subject an effective amount of an immunostimulatory oligonucleotide, wherein the oligonucleotide is 8-100 nucleotides long and comprises a mitogenic CpG motif 5′ X 1 X 2 CGX 3 X 4  3′, wherein C and G are unmethylated and X 1 , X 2 , X 3 , and X 4  are nucleotides, before administering a vaccine to the subject, to boost the subject's immune system and thereby effect an improved response to the vaccine.  
     
     
         20 . The method of  claim 19 , wherein the improved response is a Th1 response.  
     
     
         21 . The method of  claim 19 , wherein the improved response includes stimulating an antibody response in the subject.  
     
     
         22 . The method of  claim 19 , wherein the improved response includes increased expression of interferon-gamma.  
     
     
         23 . The method of  claim 19 , wherein the improved response includes a cytotoxic T lymphocyte (CTL) response.  
     
     
         24 . The method of  claim 19 , wherein the vaccine is minimally comprised of an antigen, wherein the antigen is selected from the group consisting of proteins, polysaccharides, polysaccharide conjugates, glycolipids, viruses, bacteria, fungi, parasites, allergens, and antigens-derived from an infectious organism.  
     
     
         25 . The method of  claim 24 , wherein the infectious organism is selected from the group consisting of infectious viruses, infectious bacteria, mycobacteria, infectious fungi, and parasites.  
     
     
         26 . The method of  claim 19 , wherein the immunostimulatory oligonucleotide is a DNA or RNA oligonucleotide comprising an umethylated cytosine-guanine (CpG) dinucleotide.  
     
     
         27 . The method of  claim 19 , wherein the CpG motif is selected from a group consisting of AACGTT, AGCGTT, GACGTT, GGCGTT, GTCGTT, GTCGCT, GGCGCT, GACGCT, and AACGCT.  
     
     
         28 . The method of  claim 19 , wherein the immunostimulatory oligonucleotide comprises a mitogenic CpG motif 5′ X 1 X 2 CGX 3 X 4  3′, wherein X 1 X 2  are nucleotides selected from GpT, GpG, GpA, and ApA, and wherein X 3 X 4  are nucleotides selected from TpT, CpT, and GpT.  
     
     
         29 . The method of  claim 19 , wherein the immunostimulatory oligonucleotide comprises a phosphorothioate or phosphorodithioate backbone modification.  
     
     
         30 . The method of  claim 19 , wherein the immunostimulatory oligonucleotide is administered via a systemic route.  
     
     
         31 . The method of  claim 30 , wherein the systemic route is subcutaneous or intravenous.