CpG-OLIGODEOXYNUCLEOTIDE, IMMUNOGENIC COMPOSITION COMPRISING THE SAME, AND METHODS FOR PREPARING THE COMPOSITION AND STIMULATING IMMUNE RESPONSE THEREBY

Abstract

CpG-oligodeoxynucleotides (CpG-ODN), as potent immune stimuli developed for using as adjuvant in different species, are disclosed herein. TLR9 is the cellular receptor for CpG-ODN, and current developed CpG-ODN has low activity to rabbit TLR9. Here, a type of CpG-ODN containing a GACGTT or AACGTT motif in about 11-14 deoxynucleotides was demonstrated to have potent immunostimulatory activity to rabbit TLR9, and capable of boosting a less toxic and potent antibody response in rabbits.

What is claimed is: 
     
         1 . A CpG-oligodeoxynucleotides (CpG-ODN) for eliciting a TLR9-activated immune response in a host, comprising GACGTT or AACGTT motif in 11-14 nucleotides. 
     
     
         2 . The CpG-ODN of  claim 1 , wherein the CpG-ODN consists of 11-12 nucleotides. 
     
     
         3 . The CpG-ODN of  claim 2 , wherein the CpG-ODN is selected from the group consisting of the nucleotide sequences of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6. 
     
     
         4 . The CpG-ODN of  claim 1 , wherein the CpG-ODN is the nucleotide sequence of SEQ ID NO: 1. 
     
     
         5 . The CpG-ODN of  claim 1 , wherein the host is mouse or rabbit. 
     
     
         6 . The CpG-ODN of  claim 1 , wherein the GACGTT or AACGTT motif is not located at N-terminal or C-terminal of the CpG-ODN. 
     
     
         7 . An immunogenic composition for eliciting a TLR9-activated immune response in a host, comprising an antigen and the CpG-ODN of  claim 1 . 
     
     
         8 . The immunogenic composition of  claim 7 , wherein the host is mouse or rabbit. 
     
     
         9 . The immunogenic composition of  claim 7 , wherein a ratio between the antigen and the CpG-ODN of  claim 1  is in a range from 3:50 to 10:50. 
     
     
         10 . The immunogenic composition of  claim 7 , further comprising an aluminum hydroxide gel. 
     
     
         11 . The immunogenic composition of  claim 10 , wherein a concentration of the aluminum hydroxide gel is in a range of 0.2-1% (V/V). 
     
     
         12 . A method of preparing an immunogenic composition for stimulating a TLR9-activated immune response or enhancing a TLR9-activated immune response to an antigen, comprising mixing an effective amount of the CpG-ODN of  claim 1  with an antigen and a suitable excipient. 
     
     
         13 . The method of  claim 12 , wherein a ratio between the antigen and the CpG-ODN is in a range from 3:50 to 10:50. 
     
     
         14 . The method of  claim 12 , further comprising mixing the CpG-ODN with an aluminum hydroxide gel. 
     
     
         15 . The method of  claim 14 , wherein a concentration of the aluminum hydroxide gel is in a range of 0.2-1% (V/V). 
     
     
         16 . A method of stimulating a TLR9-activated immune response or enhancing a TLR9-activated immune response to an antigen, comprising administering to a host an effective amount of the immunogenic composition of  claim 7 . 
     
     
         17 . The method of  claim 16 , wherein the host is mouse or rabbit. 
     
     
         18 . The method of  claim 16 , wherein the administering comprises subcutaneous injection.