Home » Key Scientific Articles » Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses.

Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses.

Chuang TH1, Lai CY2, Tseng PH3, Yuan CJ4, Hsu LC5.

PLoS One. 2014 ;9(9):e108808.

 

1Immunology Research Center, National Health Research Institutes, Miaoli, Taiwan; Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.and

2Immunology Research Center, National Health Research Institutes, Miaoli, Taiwan.and

3Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.and

4Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.and

5Institute of Molecular Medicine, National Taiwan University, Taipei, Taiwan.

 

Abstract

CpG-oligodeoxynucleotides (CpG-ODN) are potent immune stimuli being developed for use as adjuvants in different species. Toll-like receptor 9 (TLR9) is the cellular receptor for CpG-ODN in mammalian cells. The CpG-ODN with 18-24 deoxynucleotides that are in current use for human and mouse cells, however, have low activity with rabbit TLR9. Using a cell-based activation  assay, we developed a type of CpG-ODN containing a GACGTT or AACGTT motif in 12 phosphorothioate-modified deoxynucleotides with potent stimulatory activity for rabbit TLR9. The developed CpG-ODN have higher activities than other developed CpG-ODN in eliciting antigen-nonspecific  immune responses in rabbit splenocytes. When mixed with an NJ85 peptide derived from rabbit hemorrhagic disease virus, they had potent activities to boost an antigen-specific T cell activation and antibody production in rabbits. Compared to Freund’s adjuvant, the developed CpG-ODN are capable of boosting a potent and less toxic antibody response. The results of this study suggest that both the choice of CpG-motif and its length are important factors for CpG-ODN to effectively activate rabbit TLR9 mediated immune responses.

Go To PubMed