Immunotherapeutic uses of CpG oligodeoxynucleotides (original) (raw)
Marrack, P. & Kappler, J. Subversion of the immune system by pathogens. Cell76, 323–332 (1994). ArticleCASPubMed Google Scholar
Medzhitov, R. & Janeway, C. A. Innate immunity, impact on the adaptive immune response. Curr. Opin. Immunol.9, 4–9 (1997). ArticleCASPubMed Google Scholar
Medzhitov, R. & Janeway, C. A. Innate immunity, the virtues of a nonclonal system of recognition. Cell91, 295–298 (1998). Article Google Scholar
Paul, W. E. (ed.) in Fundamental Immunology 1–20 (Raven Press, New York, 2003). Google Scholar
Underhill, D. M. & Ozinsky, A. Toll-like receptors, key mediators of microbe detection. Curr. Opin. Immunol.14, 103–110 (2002). ArticleCASPubMed Google Scholar
Razin, A. & Friedman, J. DNA methylation and its possible biological roles. Prog. Nucl. Acid Res.25, 33–52 (1981). ArticleCAS Google Scholar
Cardon, L. R., Burge, C., Clayton, D. A. & Karlin, S. Pervasive CpG suppression in animal mitochondrial genomes. Proc. Natl Acad. Sci. USA91, 3799–3803 (1994). ArticleCASPubMedPubMed Central Google Scholar
Hemmi, H. et al. A Toll-like receptor recognizes bacterial DNA. Nature408, 740–745 (2000). This paper shows that Toll-like receptor 9 (TLR9) mediates CpG recognition in mice. ArticleCASPubMed Google Scholar
Takeshita, F. et al. Cutting Edge, role of toll-like receptor 9 in CpG DNA-induced activation of human cells. J. Immunol.167, 3555–3558 (2001). The authors show that TLR9 mediates CpG recognition in humans, and that CpG DNA co-localizes with TLR9 in endosomal vesicles. ArticleCASPubMed Google Scholar
Bauer, S. et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl Acad. Sci. USA98, 9237–9242 (2001). ArticleCASPubMedPubMed Central Google Scholar
Wagner, H. Bacterial CpG-DNA activates immune cells to signal 'infectious danger'. Adv. Immunol.73, 329–368 (1999). ArticleCASPubMed Google Scholar
Yamamoto, S. et al. Antitumor effect of nucleic acid fraction from bacteria. Proc. Jpn. Soc. Immunol.48, 272–281 (1989). Google Scholar
Yamamoto, S. et al. Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN and augment IFN-mediated natural killer activity. J. Immunol.148, 4072–4076 (1992). CASPubMed Google Scholar
Krieg, A. M. et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature374, 546–548 (1995). This work was the first to identify unmethylated CpG motifs as crucial mediators of immune activation. Studies showed that B cells responded to CpG motifs by proliferating and secreting immunoglobulin. ArticleCASPubMed Google Scholar
Klinman, D. M., Yi, A., Beaucage, S. L., Conover, J. & Krieg, A. M. CpG motifs expressed by bacterial DNA rapidly induce lymphocytes to secrete IL-6, IL-12 and IFNγ. Proc. Natl Acad. Sci. USA93, 2879–2883 (1996). The first work to establish that unmethylated CpG motifs elicited a complex immunomodulatory cascade that included the production of T helper 1 (TH1)-type and pro-inflammatory cytokines. ArticleCASPubMedPubMed Central Google Scholar
Jahrsdorfer, B. & Weiner, G. J. CpG oligodeoxynucleotides for immune stimulation in cancer immunotherapy. Curr. Opin. Investig. Drugs4, 686–690 (2003). PubMed Google Scholar
Carpentier, A. F., Auf, G. & Delattre, J. Y. CpG-oligonucleotides for cancer immunotherapy, review of the literature and potential applications in malignant glioma. Front Biosci.8, 115–127 (2003). Article Google Scholar
Ishii, K. J. et al. Potential role of phosphatidylinositol 3 kinase, rather than DNA-dependent protein kinase, in CpG DNA-induced immune activation. J. Exp. Med.196, 269–274 (2002). ArticleCASPubMedPubMed Central Google Scholar
Yi, A. K. et al. CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species. J. Immunol.160, 4755–4761 (1998). CASPubMed Google Scholar
Hacker, H. et al. CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J.17, 6230–6540 (1998). ArticleCASPubMedPubMed Central Google Scholar
Takeshita, F., Ishii, K. J., Ueda, A., Ishigatsubo, Y. & Klinman, D. M. Positive and negative regulatory elements contribute to CpG oligonucleotide-mediated regulation of human IL-6 gene expression. Eur. J. Immunol.30, 108–116 (2000). ArticleCASPubMed Google Scholar
Yamamoto, M. et al. Cutting edge, a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-β promoter in the Toll-like receptor signaling. J. Immunol.169, 6668–6672 (2002). ArticleCASPubMed Google Scholar
Takeshita, F. & Klinman, D. M. CpG ODN-mediated regulation of IL-12 p40 transcription. Eur. J. Immunol.30, 1967–1976 (2000). ArticleCASPubMed Google Scholar
Hacker, H. et al. Immune cell activation by bacterial CpG-DNA through myeroid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6. J. Exp. Med.192, 595–600 (2000). This paper describes much of the intracellular signalling cascade that is triggered by the interaction of CpG DNA with TLR9. ArticleCASPubMedPubMed Central Google Scholar
Aderem, A. & Ulevitch, R. J. Toll-like receptors in the induction of the innate immune response. Nature406, 782–787 (2000). ArticleCASPubMed Google Scholar
Ishii, K. J. et al. CpG-activated plasmacytoid dendritic cells protect against lethal Listeria monocytogenes infection. J. Immunol. (in the press).
Gursel, M., Verthelyi, D., Gursel, I., Ishii, K. J. & Klinman, D. M. Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotides. J. Leuk. Biol.71, 813–820 (2002). CAS Google Scholar
Hornung, V. et al. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol.168, 4531–4537 (2002). ArticleCASPubMed Google Scholar
Sun, S., Zhang, X., Tough, D. F. & Sprent, J. Type I interferon-mediated stimulation of T cells by CpG DNA. J. Exp. Med.188, 2335–2342 (1998). ArticleCASPubMedPubMed Central Google Scholar
Stacey, K. J., Sweet, M. J. & Hume, D. A. Macrophages ingest and are activated by bacterial DNA. J. Immunol.157, 2116–2120 (1996). CASPubMed Google Scholar
Ballas, Z. D., Rasmussen, W. L. & Krieg, A. M. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J. Immunol.157, 1840–1847 (1996). CASPubMed Google Scholar
Roman, M. et al. Immunostimulatory DNA sequences function as T helper-1 promoting adjuvants. Nature Med.3, 849–854 (1997). ArticleCASPubMed Google Scholar
Halpern, M. D., Kurlander, R. J. & Pisetsky, D. S. Bacterial DNA induces murine interferon-γ production by stimulation of IL-12 and tumor necrosis factor-α. Cell Immunol.167, 72–78 (1996). ArticleCASPubMed Google Scholar
Rankin, R. et al. CpG motif identification for veterinary and laboratory species demonstrates that sequence recognition is highly conserved. Antisense Nucl. Acid Drug Dev.11, 333–340 (2001). ArticleCAS Google Scholar
Verthelyi, D., Ishii, K. J., Gursel, M., Takeshita, F. & Klinman, D. M. Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs. J. Immunol.166, 2372–2377 (2001). This is the first work to demonstrate that distinct types of CpG oligodeoxynucleotide (ODN) exist, and that human immune cells are differentially responsive to these different ODNs. ArticleCASPubMed Google Scholar
Krug, A. et al. Identification of CpG oligonucleotide sequences with high induction of IFNα/β in plasmacytoid dendritic cells. Eur. J. Immunol.31, 2154–2163 (2001). ArticleCASPubMed Google Scholar
Kadowaki, N. et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J. Exp. Med.194, 863–869 (2001). ArticleCASPubMedPubMed Central Google Scholar
Krug, A. et al. Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. Eur. J. Immunol.31, 3026–3037 (2001). ArticleCASPubMed Google Scholar
Bauer, M. et al. Bacterial CpG DNA triggers activation and maturation of human CD11c−, CD123+ dendritic cells. J Immunol.166, 5000–5007 (2001). ArticleCASPubMed Google Scholar
Hartmann, G. et al. Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-α induction in plasmacytoid dendritic cells. Eur. J. Immunol.33, 1633–1641 (2003). ArticleCASPubMed Google Scholar
Marshall, J. D. et al. Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions. J. Leukoc. Biol.73, 781–792 (2003). ArticleCASPubMed Google Scholar
Hartmann, G. & Krieg, A. M. Mechanism and function of a newly identified CpG DNA motif in human primary B cells. J. Immunol.164, 944–952 (2000). ArticleCASPubMed Google Scholar
Verthelyi, D. et al. CpG oligodeoxynucleotides as vaccine adjuvants in primates. J. Immunol.168, 1659–1663 (2002). ArticleCASPubMed Google Scholar
Davis, H. L. et al. CpG DNA overcomes hyporesponsiveness to hepatitis B vaccine in orangutans. Vaccine18, 1920–1924 (2000). ArticleCASPubMed Google Scholar
Verthelyi, D. & Klinman, D. M. Immunoregulatory activity of CpG oligonucleotides in humans and nonhuman primates. Clin. Immunol.109, 64–71 (2003). ArticleCASPubMed Google Scholar
Broide, D. H. et al. Systemic administration of immunostimulatory DNA sequences mediates reversible inhibition of TH2 responses in a mouse model of asthma. J. Clin. Immunol.21, 175–182 (2001). ArticleCASPubMed Google Scholar
Kanellos, T. S. et al. Mammalian granulocyte–macrophage colony stimulating factor and some CpG motifs have an effect on the immunogenicity of DNA and subunit vaccines in fish. Immunology96, 507–510 (1999). ArticleCASPubMedPubMed Central Google Scholar
Gomis, S. et al. Protection of chickens against Escherichia coli infections by DNA containing CpG motifs. Infect. Immun.71, 857–863 (2003). ArticleCASPubMedPubMed Central Google Scholar
Pyles, R. B. et al. Use of immunostimulatory sequence-containing oligonucleotides as topical therapy for genital herpes simplex virus type 2 infection. J. Virol.76, 11387–11396 (2002). ArticleCASPubMedPubMed Central Google Scholar
Ashkar, A. A., Bauer, S., Mitchell, W. J., Vieira, J. & Rosenthal, K. L. 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. Virol.77, 8948–8956 (2003). ArticleCASPubMedPubMed Central Google Scholar
Klinman, D. M., Conover, J. & Coban, C. Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection. Infect. Immun.67, 5658–5663 (1999). CASPubMedPubMed Central Google Scholar
Krieg, A. M., Homan, L. L., Yi, A. K. & Harty, J. T. CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge. J. Immunol.161, 2428–2434 (1998). CASPubMed Google Scholar
Walker, P. S. et al. Immunostimulatory oligodeoxynucleotides promote protective immunity and provide systemic therapy for leishmaniasis via IL-12 and IFN-γ dependent mechanisms. Proc. Natl Acad. Sci. USA96, 6970–6975 (1999). ArticleCASPubMedPubMed Central Google Scholar
Elkins, K. L., Rhinehart-Jones, T. R., Stibitz, S., Conover, J. S. & Klinman, D. M. Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria. J. Immunol.162, 2291–2298 (1999). CASPubMed Google Scholar
Zimmermann, S. et al. CpG oligodeoxynucleotides trigger protective and curative TH1 responses in lethal murine Leishmaniasis. J. Immunol.160, 3627–3630 (1998). This work was the first to establish that CpG ODNs could be used to increase host resistance to infectious pathogens. CASPubMed Google Scholar
Klinman, D. M. Therapeutic applications of CpG-containing oligodeoxynucleotides. Antisense Nucl. Acid Drug Dev.8, 181–184 (1998). ArticleCAS Google Scholar
Chiaramonte, M. G., Hesse, M., Cheever, A. W. & Wynn, T. A. CpG Oligonucleotides can prophylactically immunize against TH2-mediated schistosome egg induced pathology by an IL-12 independent mechanism. J. Immunol.164, 973–985 (2000). ArticleCASPubMed Google Scholar
Yamamoto, T., Yamamoto, S., Katoaka, T. & Tokunaga, T. Lipofection of synthetic oligodeoxyribonucleotide having a palindromic sequence of AACGTT to murine splenocytes enhances IFN production and natural killer activity. Microbiol. Immunol.38, 831–836 (1994). ArticleCASPubMed Google Scholar
Klinman, D. M., Barnhart, K. M. & Conover, J. CpG motifs as immune adjuvants. Vaccine17, 19–25 (1999). ArticleCASPubMed Google Scholar
Pacanowski, J. et al. Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection. Blood98, 3016–3021 (2001). ArticleCASPubMed Google Scholar
Azzoni, L. et al. Sustained impairment of IFNγ secretion in suppressed HIV-infected patients despite mature NK cell recovery, evidence for a defective reconstitution of innate immunity. J. Immunol.168, 5764–5770 (2002). ArticleCASPubMed Google Scholar
Chehimi, J. et al. Persistent decreases in blood plasmacytoid dendritic cell number and function despite effective highly active antiretroviral therapy and increased blood myeloid dendritic cells in HIV-infected individuals. J. Immunol.168, 4796–4801 (2002). ArticleCASPubMed Google Scholar
Corbett, E. L. et al. HIV-1/AIDS and the control of other infectious diseases in Africa. Lancet359, 2177–2187 (2002). ArticlePubMed Google Scholar
Verthelyi, D. et al. CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection. J. Immunol.170, 4717–4723 (2003). ArticleCASPubMed Google Scholar
Weinberg, E. D. Pregnancy-associated depression of cell-mediated immunity. Rev. Infect. Dis.6, 814–831 (1984). ArticleCASPubMed Google Scholar
Priddy, K. D. Immunologic adaptations during pregnancy. J. Obstet. Gynecol. Neonatal Nurs.26, 388–394 (1997). ArticleCASPubMed Google Scholar
Wegmann, T. G., Lin, H., Guilbert, L. & Mosmann, T. R. Bidirectional cytokine interactions in the maternal–fetal relationship, is successful pregnancy a TH2 phenomenon? Immunol. Today14, 353–356 (1993). ArticleCASPubMed Google Scholar
Lin, H., Mosmann, T. R., Guilbert, L., Tuntipopipat, S. & Wegmann, T. G. Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J. Immunol.151, 4562–4573 (1993). CASPubMed Google Scholar
Raghupathy, R. TH1-type immunity is incompatible with successful pregnancy. Immunol. Today18, 478–482 (1997). ArticleCASPubMed Google Scholar
Sano, M., Mitsuyama, M., Watanabe, Y. & Nomoto, K. Impairment of T cell-mediated immunity to Listeria monocytogenes in pregnant mice. Microbiol. Immunol.30, 165–176 (1986). ArticleCASPubMed Google Scholar
Krishnan, L. et al. Pregnancy impairs resistance of C57BL/6 mice to Leishmania major infection and causes decreased antigen-specific IFN-γ response and increased production of T helper 2 cytokines. J. Immunol.156, 644–652 (1996). CASPubMed Google Scholar
Ito, S., Ishii, K., Shirot, H. & Klinman, D. M. CpG oligodeoxynucleotides improve the survival of pregnant and fetal mice following Listeria monocytogenes infection. Infect. Immunol. (in the press).
Amaral, V. F. et al. Leishmania amazonensis: the asian rhesus macaques (Macaca mulata) as an experimental model for the study of cutaneous leishmaniasis. Exp. Parasitol.82, 34–44 (1996). ArticleCASPubMed Google Scholar
Equils, O. et al. Toll-like receptor 2 (TLR2) and TLR9 signaling results in HIV-long terminal repeat trans-activation and HIV replication in HIV-1 transgenic mouse spleen cells, implications of simultaneous activation of TLRs on HIV replication. J. Immunol.170, 5159–5164 (2003). ArticleCASPubMed Google Scholar
Olbrich, A. R., Schimmer, S. & Dittmer, U. Preinfection treatment of resistant mice with CpG oligodeoxynucleotides renders them susceptible to friend retrovirus-induced leukemia. J. Virol.77, 10658–10662 (2003). ArticleCASPubMedPubMed Central Google Scholar
Gursel, I., Gursel, M., Ishii, K. J. & Klinman, D. M. Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of CpG oligonucleotides. J. Immunol.167, 3324–3328 (2001). ArticleCASPubMed Google Scholar
Davis, H. L. et al. CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. J. Immunol.160, 870–876 (1998). CASPubMed Google Scholar
Shirota, H. et al. Novel roles of CpG oligodeoxynucleotides as a leader for the sampling and presentation of CpG-tagged antigen by dendritic cells. J. Immunol.167, 66–74 (2001). ArticleCASPubMed Google Scholar
Moldoveanu, Z., Love-Homan, L., Huang, W. Q. & Krieg, A. M. CpG DNA, a novel immune enhancer for systemic and mucosal immunization with influenza virus. Vaccine 1216–1224 (1998).
Kovarik, J. et al. CpG oligonucleotides can cirmcuvent the TH2 polorization of neonatal responses to vaccines but fail to fully redirect TH2 responses established by neonatal priming. J. Immunol.162, 1611–1617 (1999). CASPubMed Google Scholar
McCluskie, M. J. & Davis, H. L. CpG DNA is a potent enhancer of systemic and mucosal immune responses against hepatitis B surface antigen with intranasal administration to mice. J. Immunol.161, 4463–4466 (1998). CASPubMed Google Scholar
Brazolot Millan, C. L., Weeratna, R., Krieg, A. M., Siegrist, C. A. & Davis, H. L. CpG DNA can induce strong TH1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice. Proc. Natl Acad. Sci. USA95, 15553–15558 (1998). ArticleCASPubMed Google Scholar
Eastcott, J. W. et al. Oligonucleotide containing CpG motifs enhances immune response to mucosally or systemically administered tetanus toxoid. Vaccine19, 1636–1642 (2001). ArticleCASPubMed Google Scholar
Branda, R. F. et al. Amplification of antibody production by phosphorothioate oligodeoxynucleotides. J. Lab. Clin. Med.128, 329–338 (1996). ArticleCASPubMed Google Scholar
Horner, A. A. et al. Immunostimulatory DNA is a potent mucosal adjuvant. Cell. Immunol.190, 77–82 (1998). ArticleCASPubMed Google Scholar
McCluskie, M. J. & Davis, H. L. Oral, intrarectal and intranasal immunizations using CpG and non-CpG oligodeoxynucleotides as adjuvants. Vaccine19, 413–422 (2000). ArticleCASPubMed Google Scholar
Jones, T. R. et al. Synthetic oligodeoxynucleotides containing CpG motifs enhance immunogenic vaccine in Aotus monkeys. Vaccine17, 3065–3071 (1999). This report demonstrates that CpG ODNs designed for human use could act as immune adjuvants in non-human primates. ArticleCASPubMed Google Scholar
Klinman, D. M., Xie, H., Little, S. F., Currie, D. & Ivins, B. CpG Oligonucleotides improve the protective immune response induced by the anthrax vaccination of rhesus macaques. Vaccine (in the press).
von Stebut, E. et al. Leishmania major infected murine langerhans cell-like dendritic cells from susceptible mice release IL-12 after infection and vaccinate against experimental cutaneous leishmaniasis. Eur. J. Immunol.30, 3498–3506 (2000). ArticleCASPubMed Google Scholar
Prince, G. A. et al. Immunoprotective activity and safety of a respiratory syncytial virus vaccine, mucosal delivery of fusion glycoprotein with a CpG oligodeoxynucleotide adjuvant. J. Virol.77, 13156–13160 (2003). ArticleCASPubMedPubMed Central Google Scholar
Davis, H. L. Use of CpG DNA for enhancing specific immune responses. Curr. Top. Microbiol. Immunol.247, 171–184 (2000). CASPubMed Google Scholar
Sears, M. R. Worldwide trends in asthma mortality. Bull. Int. Union Tuberc. Lung Dis.66, 79–83 (1991). CASPubMed Google Scholar
Nakajima, H. et al. CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. Am. Rev. Respir. Dis.146, 374–377 (1992). ArticleCASPubMed Google Scholar
Robinson, D. S. et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N. Engl. J. Med.326, 298–304 (1992). ArticleCASPubMed Google Scholar
Nakajima, H., Iwamoto, I. & Yoshida, S. Aerosolized recombinant interferon-γ prevents antigen-induced eosinophil recruitment in mouse trachea. Am. Rev. Respir. Dis.148, 1102–1104 (1993). ArticleCASPubMed Google Scholar
Sur, S. et al. Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. J. Immunol.157, 4173–4180 (1996). CASPubMed Google Scholar
Shirakawa, T., Enomoto, T., Shimazu, S. & Hopkin, J. M. The inverse association between tuberculin responses and atopic disorder. Science275, 77–79 (1997). ArticleCASPubMed Google Scholar
Erb, K. J., Holloway, J. W., Sobeck, A., Mol, l H. & Le Gros, G. Infection of mice with _Mycobacterium bovis_-Bacillus Calmette-Guerin (BCG) suppresses allergen-induced airway eosinophilia. J. Exp. Med.187, 561–569 (1998). ArticleCASPubMedPubMed Central Google Scholar
Sur, S. et al. Long-term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J. Immunol.162, 6284–6291 (1999). CASPubMed Google Scholar
Kline, J. N. et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J. Immunol.160, 2555–2559 (1998). This work was the first to establish that the combination of CpG ODNs plus allergen had a beneficial effect on allergic asthma. CASPubMed Google Scholar
Santeliz, J. V., Van Nest, G., Traquina, P., Larsen, E. & Wills-Karp, M. Amb a 1-linked CpG oligodeoxynucleotides reverse established airway hyperresponsiveness in a murine model of asthma. J. Allergy Clin. Immunol.109, 455–462 (2002). ArticleCASPubMed Google Scholar
Horner, A. A. et al. Immunostimulatory DNA inhibits IL-4-dependent IgE synthesis by human B cells. J. Allergy Clin. Immunol.108, 417–423 (2001). ArticleCASPubMed Google Scholar
Coyle, A. J. et al. Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production, inhibition by a non-anaphylactogenic anti-IgE antibody. J. Exp. Med.183, 1303–1310 (1996). ArticleCASPubMed Google Scholar
Snapper, C. M., Peschel, C. & Paul, W. E. Interferon-γ stimulates IgG2a secretion by murine B cells stimulated with bacterial lipopolysaccharide. J. Immunol.140, 2121–2130 (1988). CASPubMed Google Scholar
Tighe, H. et al. Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity. Eur. J. Immunol.30, 1939–1947 (2000). ArticleCASPubMed Google Scholar
Tighe, H. et al. Conjugation of immunostimulatory DNA to the short ragweed allergen amb a1 enhances its immunogenicity and reduces its allergenicity. J. Allergy Clin. Immunol.106, 124–134 (2000). ArticleCASPubMed Google Scholar
Horner, A. A. et al. DNA-based vaccination reduces the risk of lethal anaphylactic hypersensitivity in mice. J. Allergy Clin. Immunol.106, 349–356 (2000). ArticleCASPubMed Google Scholar
Horner, A. A., Takabaysahi, K., Zubeldia, J. M. & Raz, E. Immunostimulatory DNA-based therapeutics for experimental and clinical allergy. Allergy57 (Suppl. 72), 24–29 (2002). ArticlePubMed Google Scholar
Horner, A. A. et al. Optimized conjugation ratios lead to allergen immunostimulatory oligodeoxynucleotide conjugates with retained immunogenicity and minimal anaphylactogenicity. J. Allergy Clin. Immunol.110, 413–420 (2002). ArticleCASPubMed Google Scholar
Horner, A. A. & Raz, E. Immunostimulatory sequence oligodeoxynucleotide-based vaccination and immunomodulation, two unique but complementary strategies for the treatment of allergic diseases. J. Allergy Clin. Immunol.110, 706–712 (2002). ArticleCASPubMed Google Scholar
Gilkeson, G. S., Riuz, P., Howell, D., Lefkowith, J. B. & Pisetsky, D. S. Induction of immune-mediated glomerulonephritis in normal mice immunized with bacterial DNA. Clin. Immunol. Immunopathol.68, 283–292 (1993). ArticleCASPubMed Google Scholar
Gilkeson, G. S., Pippen, A. M. & Pisetsky, D. S. Induction of cross-reactive anti-dsDNA antibodies in preautoimmune NZB/NZW mice by immunization with bacterial DNA. J. Clin. Invest.95, 1398–1402 (1995). ArticleCASPubMedPubMed Central Google Scholar
Steinberg, A. D., Krieg, A. M., Gourley, M. F. & Klinman, D. M. Theoretical and experimental approaches to generalized autoimmunity. Immunol. Rev.118, 129–163 (1990). ArticleCASPubMed Google Scholar
Klinman, D. M. Polyclonal B cell activation in lupus-prone mice precedes and predicts the development of autoimmune disease. J. Clin. Invest.86, 1249–1254 (1990). ArticleCASPubMedPubMed Central Google Scholar
Linker-Israeli, M. et al. Elevated levels of endogenous IL-6 in systemic lupus erythematosus. J. Immunol.147, 117–123 (1991). CASPubMed Google Scholar
Krieg, A. M. CpG DNA, a pathogenic factor in systemic lupus erythematosus? J. Clin. Immunol.15, 284–292 (1995). ArticleCASPubMed Google Scholar
Yi, A. -K., Hornbeck, P., Lafrenz, D. E. & Krieg, A. M. CpG DNA rescue of murine B lymphoma cells from anti-IgM induced growth arrest and programmed cell death is associated with increased expression of c-Myc and Bcl-xl. J. Immunol.157, 4918–4925 (1996). CASPubMed Google Scholar
Katsumi, A. et al. Humoral and cellural immunity to an encoded protein induced by direct DNA injection. Hum. Gene Ther.5, 1335–1339 (1994). ArticleCASPubMed Google Scholar
Gilkeson, G. S. et al. Effects of bacterial DNA on cytokine production by (NZB/NZW)F1 mice. J. Immunol.161, 3890–3895 (1998). CASPubMed Google Scholar
Segal, B. M., Klinman, D. M. & Shevach, E. M. Microbial products induce autoimmune disease by an IL-12 dependent process. J. Immunol.158, 5087–5091 (1997). CASPubMed Google Scholar
Segal, B. M., Chang, J. T. & Shevach, E. M. CpG oligonucleotides are potent adjuvants for the activation of autoreactive encephalotogenic T cells in vivo. J. Immunol.164, 5683–5688 (2000). ArticleCASPubMed Google Scholar
Bachmaier, K. et al. Chlamydia infections and heart disease linked through antigenic mimicry. Science283, 1335–1339 (1999). ArticleCASPubMed Google Scholar
Zeuner, R. A., Verthelyi, D., Gursel, M., Ishii, K. J. & Klinman, D. M. Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis. Arthritis Rheum.48, 1701–1707 (2003). ArticleCASPubMed Google Scholar
Cowdery, J. S., Chace, J. H., Yi, A. -K. & Krieg, A. M. Bacterial DNA induces NK cells to produce IFNγ in vivo and increases the toxicity of lipopolysaccharides. J. Immunol.156, 4570–4575 (1996). CASPubMed Google Scholar
Hartmann, G., Krug, A., Waller, K. & Endres, S. Oligodeoxynucleotides enhance LPS-stimulated synthesis of TNF, dependence on phosphorothioate modification and reversal by heparin. Mol. Med.2, 429–438 (1996). ArticleCASPubMedPubMed Central Google Scholar
Heikenwalder, M. et al. Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nature Med.10, 187–192 (2004). ArticleCASPubMed Google Scholar
Klinman, D. M. et al. DNA vaccines, safety and efficacy issues. Springer Semin. Immunopathol.19, 245–256 (1997). ArticleCASPubMed Google Scholar
Wang, R. et al. Induction of antigen specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science282, 476–480 (1998). ArticleCASPubMed Google Scholar
Calarota, S. et al. Cellular cytotoxic response induced by DNA vaccination in HIV-1 infected patients. Lancet351, 1320–1325 (1998). ArticleCASPubMed Google Scholar
Yacyshyn, B. R. et al. Dose ranging pharmacokinetic trial of high-dose alicaforsen (intercellular adhesion molecule-1 antisense oligodeoxynucleotide) (ISIS 2302) in active Crohn's disease. Aliment. Pharmacol. Ther.16, 1761–1770 (2002). ArticleCASPubMed Google Scholar
Halperin, S. A. et al. A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant. Vaccine21, 2461–2467 (2003). ArticleCASPubMed Google Scholar
Klinman, D. M. et al. Immunotherapeutic applications of CpG-containing oligodeoxynucleotides. Drug News Perspect.13, 289–296 (2000). CASPubMed Google Scholar
Klinman, D. M. CpG DNA as a vaccine adjuvant. Expert Rev. Vacc.2, 305–315 (2003). ArticleCAS Google Scholar
Magone, M. T., Chan, C. C., Beck, L., Whitcup, S. M. & Raz, E. Systemic or mucosal administration of immunostimulatory DNA inhibits early and late phases of murine allergic conjunctivitis. Eur. J. Immunol.30, 1841–1850 (2000). ArticleCASPubMed Google Scholar
von Hunolstein, C. et al. The adjuvant effect of synthetic oligodeoxynucleotide containing CpG motif converts the anti-Haemophilus influenzae type b glycoconjugates into efficient anti-polysaccharide and anti-carrier polyvalent vaccines. Vaccine19, 3058–3066 (2001). ArticleCASPubMed Google Scholar
Temperton, N. J. et al. Enhancement of humoral immune responses to a human cytomegalovirus DNA vaccine, adjuvant effects of aluminum phosphate and CpG oligodeoxynucleotides. J. Med. Virol.70, 86–90 (2003). ArticleCASPubMed Google Scholar
Al Mariri, A. et al. Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvant. Infect. Immun.69, 4816–4822 (2001). ArticleCASPubMedPubMed Central Google Scholar
Hogarth, P. J., Jahans, K. J., Hecker, R., Hewinson, R. G. & Chambers, M. A. Evaluation of adjuvants for protein vaccines against tuberculosis in guinea pigs. Vaccine21, 977–982 (2003). ArticleCASPubMed Google Scholar
Su, Z., Tam, M. F., Jankovic, D. & Stevenson, M. M. Vaccination with novel immunostimulatory adjuvants against blood-stage malaria in mice. Infect. Immun.71, 5178–5187 (2003). ArticleCASPubMedPubMed Central Google Scholar
Mendez, S. et al. Coinjection with CpG-containing immunostimulatory oligodeoxynucleotides reduces the pathogenicity of a live vaccine against cutaneous Leishmaniasis but maintains its potency and durability. Infect. Immun.71, 5121–5129 (2003). ArticleCASPubMedPubMed Central Google Scholar
Frank, F. M. et al. Use of a purified Trypanosoma cruzi antigen and CpG oligodeoxynucleotides for immunoprotection against a lethal challenge with trypomastigotes. Vaccine22, 77–86 (2003). ArticleCASPubMed Google Scholar