Oligodeoxynucleotides(ODN) containing CpG motifs possess the ability of microbial DNA to activate the innate immune system,which limits the early spread of infectious organisms while promoting the development of adaptive immunity. CpG ODN are of promise as vaccine adjuvants and agents in the treatment of asthma, allergy, infection, and cancer. Due to evolutionary divergence in CpG recognition between species, CpG ODN active in rodents,are poorly immunostimulatory in primates. Thus, evidence that CpG ODN have therapeutic activity in mice must be confirmed in primates.In this paper,two distinct types of CpG ODN and their mode of actions will be introduced and the literature documenting their ability to act as vaccine adjuvants and immunoprotective agents in primates and in the treatment of diseases such as cancer,allergy and asthma will be reviewed. |
[1] Sparwasser T, KOCH E, VABULAS R M. Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. 1998(6). doi:10.1002/(SICI)1521-4141(199806)28:06<, 2045::AID-IMMU2045>, 3.0.CO, 2-8
[2] Verthelyi D, ISHII K J, GURSEL M. Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs. 2001(4)
[3] Krieg A M. CpG motifs in bacterial DNA and their immune effects. 2002(). doi:10.1146/annurev.immunol.20.100301.064842
[4] DALPKEe A H, ZIMMERMANN S, ALBRECHT I. Phosphodiester CpG oligonucleotides as adjuvants: polyguanosine runs enhance cellular uptake and improve immunostimulative activity of phosphodiester CpG oligonucleotides in vitro and in vivo. 2002(1). doi:10.1046/j.1365-2567.2002.01410.x
[5] Gursel M, VERTHELYI D, GURSEL I. Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide. 2002(5)
[6] Takeshita F, LEIFER C A, GURSEL I. Cutting Edge:role of toll-like receptor 9 in CpG DNA-induced activation of human cells, 2001(7)
[7] Bauer S, KIRSCHNING C J, HACKER H. Human TLR9 confers responsiveness to bacterial DNA via species specific CpG motif recognition, 2001
[8] Ahmad-Nejad P, HACKER H, RUTZ M. Bacterial CpG-DNA and lipopolysaccharides activate Tolllike receptors at distinct cellular compartments. 2002(7). doi:10.1002/1521-4141(200207)32:7<, 1958::AID-IMMU1958>, 3.0.CO, 2-U
[9] Hemmi H, KAISHO T, TAKEDA K. The roles of Toll-like receptor 9,MyD88,and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets. 2003(6)
[10] Krug A, ROTHENFUSSER S, SELINGER S. CpG-A oligonucleotides induce a monocyte-derived dendritic celllike phenotype that preferentially activates CD8 T cells. 2003(7)
[11] LEIFER C A, VERTHELYI D, KLINMAN D M. Heterogeneity in the human response to immunostimulatory CpG oligodeoxynucleotides. 2003(4)
[12] Lazarus R, KLIMECKI W T, RABY B A. Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9):frequencies,pairwise linkage disequilibrium,and haplotypes in three U.S.ethnic groups and exploratory case-control disease association studies. 2003(4). doi:10.1016/S0888-7543(2)00022-8
[13] Renshaw M, RWCKWELL J, ENGLEMAN C. Cutting edge:impaired Toll-like receptor expression and function in aging, 2002(9)
[14] Verthelyi D, KENNEY R T, SEDER R A. CpG oligodeoxynucleotides as vaccine aduvants in primates, 2002(4)
[15] KRIGE A M, DAVIS H L. Enhancing vaccines with immune stimulatory CpG DNA, 2001
[16] Gurunathan S, KLINMAN D M, SEDER R A. DNA vaccines:immunology,application,and optimization. 2000(). doi:10.1146/annurev.immunol.18.1.927
[17] HORNER A A, RAZ E. Immunostimulatory sequence oligodeoxynucleotide-based vaccination and immunomodulation: two unique but complementary strategies for the treatment of allergic diseases. 2002(5). doi:10.1067/mai.2002.129122
[18] Verthelyi D, GURSEL M, KENNEY R T. CpG oligodeoxynucleotides protect normal and SIV infected macaques from Leishmania infection. 2003(9)
[19] ZEUNER R A, KLINMAN D M, ILLEI G. Response of peripheral blood mononuclear cells from lupus patients to stimulation by CpG oligodeoxynucleotides. 2003 |
