Cpg Single Strand Deoxynucleotides for Use as Adjuvant

Abstract

The present invention provides an adjuvant, which includes at least one single strand deoxynucleotide containing a CpG dinucleotide. The single strand deoxynucleotide comprises one or more CpG dinucleotides. When used in combination with rabies vaccine, HBV vaccine or other vaccines, the adjuvant can significantly improve the immune effect of the vaccine.

1 . A single strand deoxynucleotide, comprising one or more CpG dinucleotides.  
     
     
         2 . The single strand deoxynucleotide of  claim 1 , wherein the deoxynucleotide is represented by one of the following formulas: 
 (i) (G) n (L) n X 1 X 2 CGY 1 Y 2 (M) n (G) n , wherein X 1 =A, T or G; X 2 =A or T; Y 1 =A or T; Y 2 =A, T or C; L, M=A, T, C or G; n is 0-6;    (ii) (G) n (L) n CG(XY) n CG(M) n (G) n , wherein X=A or T; Y=A or T; L, M=A, T, C or G; n is 0-6;    (iii) (TCG) n (L) n CG(M) n (G) n , wherein L, M=A, T, C or G; n is 0-6;    (iv) (TCG) n (L) n X 1 X 2 CG(M) n , wherein X 1 =A, T or G; X 2 =A or T; L, M=A, T, C or G; n is 0-6; or    (v) sequences containing TTCGTCG.    
     
     
         3 . The single strand deoxynucleotide of  claim 2 , comprising any one of SEQ ID NO: 1 to SEQ ID NO: 185.  
     
     
         4 . The single strand deoxynucleotide of  claim 3 , comprising any one of SEQ ID NO: 109, 150, 167 or 168.  
     
     
         5 . The single strand deoxynucleotide of  claim 1 , wherein bases of the deoxynucleotide are modified by one or more of the following modifications: non-sulpher modification, sulpher modification, partial sulpher modification, rare base modification, methylation modification, and other modifications where sulfhydryl, Aminolinker C6, Thiol-C6 S—S, etc. are used to couple to other substances.  
     
     
         6 . A vaccine adjuvant comprising the single strand deoxynucleotide of  claim 1 .  
     
     
         7 . The vaccine adjuvant of  claim 6 , wherein the single strand deoxynucleotide is used alone or in combination with a non-nucleic acid adjuvant including aluminum adjuvant, Freund's adjuvant, MPL, or emulsion.  
     
     
         8 . The vaccine adjuvant of  claim 6 , wherein the single strand deoxynucleotide is admixed with or chemical coupled to a vaccine, or the single strand deoxynucleotide is cloned into a DNA vaccine.  
     
     
         9 . The vaccine adjuvant of  claim 8 , wherein the vaccine is selected from the group consisting of hepatitis B virus blood-derived vaccine, hepatitis B virus genetic engineering protein vaccines, HBV virus vector vaccine, hepatitis B virus bacterium vector vaccine, hepatitis B virus transgenic plant vaccine, rabies virus blood-derived vaccine, rabies virus genetic engineering protein vaccines, rabies virus vector vaccine, rabies virus bacterium vector vaccine, and rabies virus transgenic plant vaccine, and the DNA vaccine is selected from the group consisting of hepatitis B virus DNA vaccine and rabies DNA vaccine.  
     
     
         10 . A method of improving immunogenicity of a vaccine, comprising coadministering said vaccine to a subject with at least one single strand deoxynucleotide of  claim 1  and a vaccine.  
     
     
         11 . The method of  claim 10 , further comprising administering non-nucleic acid adjuvants.  
     
     
         12 . The method of  claim 10 , wherein the subject is human.  
     
     
         13 . The method of  claim 10 , wherein the subject is a mammal.  
     
     
         14 . A method for preventing virus infection and a disease related to virus infection comprising administering to a subject in need thereof the single strand deoxynucleotide of  claim 1 .  
     
     
         15 . The method of  claim 14 , wherein the single strand deoxynucleotide is administered alone or in combination with a vaccine for preventing virus infection.  
     
     
         16 . The method of  claim 15 , wherein said administering is intramuscular, subcutaneous, mucosal, gastrointestinal, intravenous, or intraperitoneal.  
     
     
         17 . The single strand deoxynucleotide of  claim 5 , wherein said rare base modification is dI or dU.