Use of CpG oligodeoxynucleotides as immune adjuvants

被引:240
作者
Klinman, DM
Currie, D
Gursel, I
Verthelyi, D
机构
[1] US FDA, Sect Retroviral Immunol, Div Viral Prod, CBER, Bethesda, MD 20892 USA
[2] US FDA, Div Therapeut Prot, CBER, Bethesda, MD 20014 USA
关键词
D O I
10.1111/j.0105-2896.2004.00148.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs directly stimulate human B cells and plasmacytoid dendritic cells (pDCs), thereby promoting the production of T helper 1 (Th1) and pro-inflammatory cytokines and the maturation/activation of professional antigen-presenting cells. These activities enable CpG ODNs to act as immune adjuvants, accelerating and boosting antigen-specific immune responses by 5-500-fold. These effects are optimized by maintaining close physical contact between the CpG DNA and the immunogen. Animal challenge models establish that protective immunity can be accelerated and magnified by coadministering CpG DNA with vaccines. Ongoing clinical studies indicate that CpG ODNs are safe and well tolerated when administered as adjuvants to humans, and in some cases, they increase vaccine-induced immune responses.
引用
收藏
页码:201 / 216
页数:16
相关论文
共 143 条
  • [1] Toll-like receptors in the induction of the innate immune response
    Aderem, A
    Ulevitch, RJ
    [J]. NATURE, 2000, 406 (6797) : 782 - 787
  • [2] Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvant
    Al-Mariri, A
    Tibor, A
    Mertens, P
    De Bolle, X
    Michel, P
    Godefroid, J
    Walravens, K
    Letesson, JJ
    [J]. INFECTION AND IMMUNITY, 2001, 69 (08) : 4816 - 4822
  • [3] Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication, but not entry, of herpes simplex virus type 2
    Ashkar, AA
    Bauer, S
    Mitchell, WJ
    Vieira, J
    Rosenthal, KL
    [J]. JOURNAL OF VIROLOGY, 2003, 77 (16) : 8948 - 8956
  • [4] CpG DNA induces maturation of dendritic cells with distinct effects on nascent and recycling MHC-II antigen-processing mechanisms
    Askew, D
    Chu, RS
    Krieg, AM
    Harding, CV
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 165 (12) : 6889 - 6895
  • [5] Sustained impairment of IFN-γ secretion in suppressed HIV-infected patients despite mature NK cell recovery:: Evidence for a defective reconstitution of innate immunity
    Azzoni, L
    Papasavvas, E
    Chehimi, J
    Kostman, JR
    Mounzer, K
    Ondercin, J
    Perussia, B
    Montaner, LJ
    [J]. JOURNAL OF IMMUNOLOGY, 2002, 168 (11) : 5764 - 5770
  • [6] Chlamydia infections and heart disease linked through antigenic mimicry
    Bachmaier, K
    Neu, N
    de la Maza, LM
    Pal, S
    Hessel, A
    Penninger, JM
    [J]. SCIENCE, 1999, 283 (5406) : 1335 - 1339
  • [7] Ballas ZK, 1996, J IMMUNOL, V157, P1840
  • [8] DNA activates human immune cells through a CpG sequence-dependent manner
    Bauer, M
    Heeg, K
    Wagner, H
    Lipford, GB
    [J]. IMMUNOLOGY, 1999, 97 (04) : 699 - 705
  • [9] Bacterial CpG-DNA triggers activation and maturation of human CD11c-, CD123+ dendritic cells
    Bauer, M
    Redecke, V
    Ellwart, JW
    Scherer, B
    Kremer, JP
    Wagner, H
    Lipford, GB
    [J]. JOURNAL OF IMMUNOLOGY, 2001, 166 (08) : 5000 - 5007
  • [10] Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition
    Bauer, S
    Kirschning, CJ
    Häcker, H
    Redecke, V
    Hausmann, S
    Akira, S
    Wagner, H
    Lipford, GB
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) : 9237 - 9242