Immunotherapeutic uses of CpG oligodeoxynucleotides

被引:837
作者
Klinman, DM [1 ]
机构
[1] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA
关键词
D O I
10.1038/nri1329
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) that contain immunostimulatory CpG motifs trigger an immunomodulatory cascade that involves B and T cells, natural killer cells and professional antigen-presenting cells. The response to CpG ODNs skews the host's immune milieu in favour of T helper 1 (T(H)1)-cell responses and pro-inflammatory cytokine production-an effect that underlies their use as immunoprotective agents, vaccine adjuvants and anti-allergens. Preclinical studies provide evidence that CpG ODNs are effective for each of these uses. Ongoing clinical studies indicate that CpG ODN use is safe in humans, and that they modulate the immune response to co-administered allergens and vaccines.
引用
收藏
页码:248 / 257
页数:10
相关论文
共 153 条
[1]   Toll-like receptors in the induction of the innate immune response [J].
Aderem, A ;
Ulevitch, RJ .
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 [J].
Al-Mariri, A ;
Tibor, A ;
Mertens, P ;
De Bolle, X ;
Michel, P ;
Godefroid, J ;
Walravens, K ;
Letesson, JJ .
INFECTION AND IMMUNITY, 2001, 69 (08) :4816-4822
[3]   Leishmania amazonensis: The Asian rhesus macaques (Macaca mulatta) as an experimental model for study of cutaneous leishmaniasis [J].
Amaral, VF ;
Ransatto, VAO ;
ConceicaoSilva, F ;
Molinaro, E ;
Ferreira, V ;
Coutinho, SG ;
McMahonPratt, D ;
Grimaldi, G .
EXPERIMENTAL PARASITOLOGY, 1996, 82 (01) :34-44
[4]   Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication, but not entry, of herpes simplex virus type 2 [J].
Ashkar, AA ;
Bauer, S ;
Mitchell, WJ ;
Vieira, J ;
Rosenthal, KL .
JOURNAL OF VIROLOGY, 2003, 77 (16) :8948-8956
[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 [J].
Azzoni, L ;
Papasavvas, E ;
Chehimi, J ;
Kostman, JR ;
Mounzer, K ;
Ondercin, J ;
Perussia, B ;
Montaner, LJ .
JOURNAL OF IMMUNOLOGY, 2002, 168 (11) :5764-5770
[6]   Chlamydia infections and heart disease linked through antigenic mimicry [J].
Bachmaier, K ;
Neu, N ;
de la Maza, LM ;
Pal, S ;
Hessel, A ;
Penninger, JM .
SCIENCE, 1999, 283 (5406) :1335-1339
[7]  
Ballas ZK, 1996, J IMMUNOL, V157, P1840
[8]   Bacterial CpG-DNA triggers activation and maturation of human CD11c-, CD123+ dendritic cells [J].
Bauer, M ;
Redecke, V ;
Ellwart, JW ;
Scherer, B ;
Kremer, JP ;
Wagner, H ;
Lipford, GB .
JOURNAL OF IMMUNOLOGY, 2001, 166 (08) :5000-5007
[9]   Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition [J].
Bauer, S ;
Kirschning, CJ ;
Häcker, H ;
Redecke, V ;
Hausmann, S ;
Akira, S ;
Wagner, H ;
Lipford, GB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) :9237-9242
[10]   Amplification of antibody production by phosphorothioate oligodeoxynucleotides [J].
Branda, RF ;
Moore, AL ;
Lafayette, AR ;
Mathews, L ;
Hong, R ;
Zon, G ;
Brown, T ;
McCormack, JJ .
JOURNAL OF LABORATORY AND CLINICAL MEDICINE, 1996, 128 (03) :329-338