Use of CpG oligodeoxynucleotides as immunoprotective agents

被引:73
作者
Klinman, DM [1 ]
机构
[1] US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA
关键词
CpG oligodeoxynucleotide; host protection; innate immunity;
D O I
10.1517/14712598.4.6.937
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Single-stranded oligodeoxynucleotides (ODNs) synthesised to express unmethylated 'CpG motifs' mimic the ability of bacterial DNA to trigger the innate immune system. CpG ODNs stimulate cells that express Toll-like receptor 9, initiating an immunomodulatory cascade resulting in the activation of B and T lymphocytes, natural killer cells, monocytes, macrophages and dendritic cells. CpG ODNs improve the host's ability to resist infection by accelerating and improving the induction of an innate and then adaptive immune response, characterised by the production of Th1 and pro-inflammatory cytokines, chemokines; and polyreactive antibodies. Studies in rodents and non-human primates demonstrate that CpG ODNs can protect the host against bacterial, viral, fungal and parasitic infections. CpG-induced protection develops rapidly but persists for only a few weeks. Preclinical and clinical trials suggest that CpG ODNs can be used safely to activate the human immune system.
引用
收藏
页码:937 / 946
页数:10
相关论文
共 97 条
  • [31] Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration
    Heikenwalder, M
    Polymenidou, M
    Junt, T
    Sigurdson, C
    Wagner, H
    Akira, S
    Zinkernagel, R
    Aguzzi, A
    [J]. NATURE MEDICINE, 2004, 10 (02) : 187 - 192
  • [32] RECIPROCAL EXPRESSION OF INTERFERON-GAMMA OR INTERLEUKIN-4 DURING THE RESOLUTION OR PROGRESSION OF MURINE LEISHMANIASIS - EVIDENCE FOR EXPANSION OF DISTINCT HELPER T-CELL SUBSETS
    HEINZEL, FP
    SADICK, MD
    HOLADAY, BJ
    COFFMAN, RL
    LOCKSLEY, RM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 169 (01) : 59 - 72
  • [33] A Toll-like receptor recognizes bacterial DNA
    Hemmi, H
    Takeuchi, O
    Kawai, T
    Kaisho, T
    Sato, S
    Sanjo, H
    Matsumoto, M
    Hoshino, K
    Wagner, H
    Takeda, K
    Akira, S
    [J]. NATURE, 2000, 408 (6813) : 740 - 745
  • [34] Quantitative expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides
    Hornung, V
    Rothenfusser, S
    Britsch, S
    Krug, A
    Jahrsdörfer, B
    Giese, T
    Endres, S
    Hartmann, G
    [J]. JOURNAL OF IMMUNOLOGY, 2002, 168 (09) : 4531 - 4537
  • [35] Iho S, 1999, J IMMUNOL, V163, P3642
  • [36] ISHII KJ, 2004, IN PRESS J IMMUNOL
  • [37] ITO S, 2004, VACCINE, V72, P3543
  • [38] CpG DNA induces protective antiviral immune responses in Atlantic salmon (Salmo salar L.)
    Jorgensen, JB
    Johansen, LH
    Steiro, K
    Johansen, A
    [J]. JOURNAL OF VIROLOGY, 2003, 77 (21) : 11471 - 11479
  • [39] CpG oligodeoxynucleotides enhance host defense during murine tuberculosis
    Juffermans, NP
    Leemans, JC
    Florquin, S
    Verbon, A
    Kolk, AH
    Speelman, P
    van Deventer, SJH
    van der Poll, T
    [J]. INFECTION AND IMMUNITY, 2002, 70 (01) : 147 - 152
  • [40] Kanellos TS, 1999, IMMUNOLOGY, V96, P507, DOI 10.1046/j.1365-2567.1999.00771.x