Recent advances in DNA vaccines for autoimmune diseases

Expert Review of Vaccines

Volumn 8, Issue 2, 2009, Pages 239-252

  Silva, Celio L ^a,b   Bonato, Vânia L D ^a   Dos Santos Júnior, Rubens R ^a,c   Zárate Bladés, Carlos R ^a   Sartori, Alexandrina ^c  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b Farmacore Biotechnology Ltd   (Brazil)

^c SÃO PAULO STATE UNIVERSITY UNESP   (Brazil)

Author keywords

Autoimmunity; DNA vaccine; Tolerance; Treg cell

Indexed keywords

CPG OLIGODEOXYNUCLEOTIDE; DNA VACCINE; HEAT SHOCK PROTEIN; HEAT SHOCK PROTEIN 65; PLASMID DNA;

ACCURACY; ALLERGIC ENCEPHALOMYELITIS; ANTIGEN SPECIFICITY; ANTIPHOSPHOLIPID SYNDROME; ARTHRITIS; AUTOIMMUNE DISEASE; AUTOIMMUNITY; COST EFFECTIVENESS ANALYSIS; DENDRITIC CELL; DIABETES MELLITUS; DNA IMMUNIZATION; GENE EXPRESSION; GENETIC ENGINEERING; HUMAN; IMMUNE SYSTEM; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; MULTIPLE SCLEROSIS; MYCOBACTERIUM; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; REGULATORY T LYMPHOCYTE; REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; VACCINATION;

AUTOIMMUNE DISEASES; BACTERIAL PROTEINS; CHAPERONINS; HUMANS; VACCINES, DNA;

EID: 60149103797     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/14760584.8.2.239     Document Type: Review

References (147)

1. Fernando MM, Stevens CR, Walsh EC et al. Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet. 4(4), E1000024 (2008).
2. Kohm AP, Fuller KG, Miller SD. Mimicking the way to autoimmunity: an evolving theory of sequence and structural homology. Trends Microbiol. 11(3), 101-105 (2003).
3. Horwitz MS, Ilic A, Fine C, Rodriguez E, Sarvetnick N. Presented antigen from damaged pancreatic β cells activates autoreactive T cells in virus-mediated autoimmune diabetes. J. Clin. Invest. 109(1), 79-87 (2002).
4. Garn H, Renz H. Epidemiological and immunological evidence for the hygiene hypothesis. Immunobiology 212(6), 441-452 (2007).
5. Zaccone P, Fehervari Z, Phillips JM, Dunne DW, Cooke A. Parasitic worms and inflammatory diseases. Parasite Immunol. 28(10), 515-523 (2006).
6. Sewell DL, Reinke EK, Hogan LH, Sandor M, Fabry Z. Immunoregulation of CNS autoimmunity by helminth and mycobacterial infections. Immunol. Lett. 82(1-2), 101-110 (2002).
7. Rook GA. The hygiene hypothesis and the increasing prevalence of chronic inflammatory disorders. Trans. R. Soc. Trop. Med. Hyg. 101(11), 1072-1074 (2007).
8. Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 423(6937), 356-361 (2003).
9. Lebre MC, Tak PP. Dendritic cell subsets: their roles in rheumatoid arthritis. Acta Rheumatol. Port. 33(1), 35-45 (2008).
10. Sato K. Th17 cells and rheumatoid arthritis - from the standpoint of osteoclast differentiation. Allergol. Int. 57(2), 109-114 (2008).
11. + regulatory T cells. Arthritis Rheum. 52(7), 2212-2221 (2005).
12. + regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease. Arthritis Res. Ther. 6(4), R335-R346 (2004).
13. + T cells in the peripheral blood and synovial fluid of patients with rheumatoid arthritis. Scand. J. Immunol. 62(3), 312-317 (2005).
14. Chentoufi AA, Binder NR, Berka N, Abunadi T, Polychronakos C. Advances in Type I diabetes associated tolerance mechanisms. Scand. J. Immunol. 68(1), 1-11 (2008).
15. Jaeckel E, Mpofu N, Saal N, Manns MP. Role of regulatory T cells for the treatment of Type 1 diabetes mellitus. Horm. Metab. Res. 40(2), 126-136 (2008).
16. Bluestone JA, Tang Q, Sedwick CE. T regulatory cells in autoimmune diabetes: past challenges, future prospects. J. Clin. Immunol. 28(6), 677-684 (2008).
17. + regulatory T cells in NOD mice that can prevent diabetes development. PLoS ONE 3(11), E3739 (2008).
18. Walker LS. Natural Treg in autoimmune diabetes: all present and correct? Expert Opin. Biol. Ther. 8(11), 1691-1703 (2008).
19. + regulatory T cells. J. Immunol. 181(10), 7350-7355 (2008).
20. Dhib-Jalbut S. Pathogenesis of myelin/oligodendrocyte damage in multiple sclerosis. Neurology 68(22 Suppl. 3), S13-S21 (2007).
21. Holmoy T, Hestvik AL. Multiple sclerosis: immunopathogenesis and controversies in defining the cause. Curr. Opin. Infect. Dis. 21(3), 271-278 (2008).
22. Zozulya AL, Wiendl H. The role of regu latory T cells in multiple sclerosis. Nat. Clin. Pract. Neurol. 4(7), 384-398 (2008).
23. Mauri C, Ehrenstein MR. The 'short' history of regulatory B cells. Trends Immunol. 29(1), 34-40 (2008).
24. Jolicoeur C, Hanahan D, Smith KM. T-cell tolerance toward a transgenic β-cell antigen and transcription of endogenous pancreatic genes in thymus. Proc. Natl Acad. Sci. USA 91(14), 6707-6711 (1994).
25. Gotter J, Brors B, Hergenhahn M, Kyewski B. Medullary epithelial cells of the human thymus express a highly diverse selection of tissue-specific genes colocalized in chromosomal clusters. J. Exp. Med. 199(2), 155-166 (2004).
26. Nemazee D. Receptor editing in lymphocyte development and central tolerance. Nat. Rev. Immunol. 6(10), 728-740 (2006).
27. Roncarolo MG, Battaglia M. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat. Rev. Immunol. 7(8), 585-598 (2007).
28. + regulatory thymocytes. Microbes Infect. 7(7-8), 1017-1022 (2005).
29. + T cells. Biochem. Biophys. Res. Commun. 369(4), 1134-1138 (2008).
30. + CD25- T cells is associated with the expression of CTLA-4 not FoxP3. J. Immunol. 181(3), 1683-1691 (2008).
31. Mazzucchelli R, Hixon JA, Spolski R et al. Development of regulatory T cells requires IL-7Rα stimulation by IL-7 or TSLP. Blood 112(8), 3283-3292 (2008).
32. + regulatory T cells. Nat. Immunol. 4(4), 330-336 (2003).
33. Hori S, Nomura T, Sakaguchi S. Control of regu latory T cell development by the transcription factor Foxp3. Science 299(5609), 1057-1061 (2003).
34. + T regulatory cells. Nat. Immunol. 4(4), 337-342 (2003).
35. Roncarolo MG, Gregori S. Is FOXP3 a bona fide marker for human regulatory T cells? Eur. J. Immunol. 38(4), 925-927 (2008).
36. Coombes JL, Siddiqui KR, Arancibia-Carcamo CV et al. A functionally specialized population of mucosal CD103-DCs induces Foxp3-regulatory T cells via a TGFβ and retinoic acid-dependent mechanism. J. Exp. Med. 204, 1757-1764 (2007).
37. + regulatory T cells. J. Immunol. 181(10), 6923-6933 (2008).
38. + regulatory T cells. Front. Biosc. 11, 1014-1023 (2006).
39. Scheffold A, Murphy KM, Höfer T. Competition for cytokines: Treg cells take all. Nat. Immunol. 8(12), 1285-1287 (2007).
40. Sojka DK, Huang YH, Fowell DJ. Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target. Immunology 124(1), 13-22 (2008).
41. Minguet S, Huber M, Rosenkranz L, Schamel WW, Reth M, Brummer T. Adenosine and cAMP are potent inhibitors of the NF-κ B pathway downstream of immunoreceptors. Eur. J. Immunol. 35(1), 31-41 (2005).
42. Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J. Exp. Med. 190(7), 995-1004 (1999).
43. + T cells. J. Exp. Med. 183(6), 2669-2674 (1996).
44. + T cells. Nat. Immunol. 8(12), 1353-1362 (2007).
45. Miller SD, Turley DM, Podojil JR. Antigen-specific tolerance strategies for the prevention and treatment of autoimmune disease. Nat. Rev. Immunol. 7(9), 665-677 (2007).
46. Stewart AJ, Devlin PM. The history of the smallpox vaccine. J. Infect. 52(5), 329-334 (2006).
47. Schwartz M. Institut Pasteur: 120 years of research in microbiology. Res. Microbiol. 159(1), 5-14 (2008).
48. Steinman RM. Dendritic cells and vaccine. Proc. (Bayl. Univ. Med. Cent.) 21(1), 3-8 (2008).
49. Wolff JA, Malone RW, Williams P et al. Direct gene transfer into mouse muscle in vivo. Science 247(4949 Pt 1), 1465-1468 (1990).
50. Ulmer JB, Donnelly JJ, Parker SE et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259(5102), 1745-1749 (1993).
51. Laddy DJ, Weiner DB. From plasmids to protection: a review of DNA vaccines against infectious diseases. Int. Rev. Immunol. 25(3-4), 99-123 (2006).
52. Lowrie DB, Silva CL, Colston MJ, Ragno S, Tascon RE. Protection against tuberculosis by a plasmid DNA vaccine. Vaccine 15(8), 834-838 (1997).
53. Lowrie DB, Tascon RE, Bonato VL et al. Therapy of tuberculosis in mice by DNA vaccination. Nature 400(6741), 269-271 (1999).
54. Kutzler MA, Weiner DB. DNA vaccines: ready for prime time? Nat. Rev. Genet. 9(10), 776-788 (2008).
55. Lu S, Wang S, Grimes-Serrano JM. Current progress of DNA vaccine studies in humans. Expert Rev. Vaccines 7(2), 175-191 (2008).
56. Basner-Tschakarjan E, Mirmohammadsadegh A, Baer A, Hengge UR. Uptake and trafficking of DNA in keratinocytes: evidence for DNA-binding proteins. Gene Ther. 11(9), 765-774 (2004).
57. Jozefowski S, Sulahian TH, Arredouani M, Kobzik L. Role of scavenger receptor M ARCO in macrophage responses to CpG oligodeoxynucleotides. J. Leukoc. Biol. 80(4), 870-879 (2006).
58. Trombone AP, Silva CL, Lima KM et al. Endocytosis of DNA-Hsp65 alters the pH of the late endosome/lysosome and interferes with antigen presentation. PLoS ONE 2(9), E923 (2007).
59. Lechardeur D, Verkman AS, Lukacs GL. Intracellular routing of plasmid DNA during non-viral gene transfer. Adv. Drug Deliv. Rev. 57(5), 755-767 (2005).
60. Lechardeur D, Lukacs GL. Nucleocytoplasmic transport of plasmid DNA: a perilous journey from the cytoplasm to the nucleus. Hum. Gene Ther. 17(9), 882-889 (2006).
61. Belakova J, Horynova M, Krupka M, Weigl E, Raska M. DNA vaccines: are they still just a powerful tool for the future? Arch. Immunol. Ther. Exp. (Warsz.) 55(6), 387-398 (2007).
62. Hemmi H, Takeuchi O, Kawai T et al. A Toll-like receptor recognizes bacterial DNA. Nature 408(6813), 740-745 (2000).
63. Latz E, Schoenemeyer A, Visintin A et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat. Immunol. 5(2), 190-198 (2004).
64. Hacker H, Vabulas RM, Takeuchi O et al. Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6. J. Exp. Med. 192(4), 595-600 (2000).
65. Takeshita F, Ishii KJ, Ueda A, Ishigatsubo Y, Klinman DM. Positive and negative regulatory elements contribute to CpG oligonucleotide-mediated regulation of human IL-6 gene expression. Eur. J. Immunol. 30(1), 108-116 (2000).
66. Takeshita F, Klinman DM. CpG ODN-mediated regulation of IL-12 p40 transcription. Eur. J. Immunol. 30(7), 1967-1976 (2000).
67. Yamamoto M, Sato S, Mori K 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(12), 6668-6672 (2002).
68. Ballas ZK, Rasmussen WL, Krieg AM. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J. Immunol. 157(5), 1840-1845 (1996).
69. Krieg AM, Yi AK, Matson S et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374(6522), 546-549 (1995).
70. Agrawal S, Kandimalla ER. Modulation of Toll-like receptor 9 responses through synthetic immunostimulatory motifs of DNA. Ann. NYAcad. Sci. 1002, 30-42 (2003).
71. Franco LH, Wowk PF, Silva CL et al. A DNA vaccine against tuberculosis based on the 65 kDa heat-shock protein differentially activates human macrophages and dendritic cells. Genet. Vaccines Ther. 6, 3 (2008).
72. Ishii KJ, Kawagoe T, Koyama S et al. TANK-biding kinase 1 delineates innate and adaptive immune responses to DNA vaccines. Nature 451, 725-729 (2008).
73. Pertmer TM, Roberts TR, Haynes JR. Influenza virus nucleoprotein-specific immunoglobulin G subclass and cytokine responses elicited by DNA vaccination are dependent on the route of vector DNA delivery. J. Virol. 70(9), 6119-6125 (1996).
74. Li L, Boussiotis VA. Physiologic regulation of central and peripheral T cell tolerance: lessons for therapeutic applications. J. Mol. Med. 84(11), 887-899 (2006).
75. Mimran A, Mor F, Carmi P, Quintana FJ, Rotter V, Cohen IR. DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response. J. Clin. Invest. 113(6), 924-932 (2004).
76. Linsen L, Somers V, Stinissen P. Immunoregulation of autoimmunity by natural killer T cells. Hum. Immunol. 66(12), 1193-1202 (2005).
77. Awasthi A, Murugaiyan G, Kuchroo VK. Interplay between effector Th17 and regulatory T cells. J. Clin. Immunol. 28(6), 660-670 (2008).
78. Nikoopour E, Schwartz JA, Singh B. Therapeutic benefits of regulating inflammation in autoimmunity. Inflamm. Allergy Drug Targets 7(3), 203-210 (2008).
79. Ferrera F, La Cava A, Rizzi M, Hahn BH, Indiveri F, Filaci G. Gene vaccination for the induction of immune tolerance. Ann. NY Acad. Sci. 1110, 99-111 (2007).
80. Harrison LC. Vaccination against self to prevent autoimmune diseases: the Type 1 diabetes model. Immunol. Cell Biol. 86, 139-145 (2008).
81. Ho PP, Higgins JP, Kidd BA et al. Tolerizing DNA vaccines for autoimmune arthritis. Autoimmunity 39(8), 675-682 (2006).
82. Tisch R, Wang B, Weaver DJ et al. Antigen-specific mediated suppression of β cell autoimmunity by plasmid DNA vaccination. J. Immunol. 166(3), 2122-2132 (2001).
83. Bot A, Smith D, Bot S et al. Plasmid vaccination with insulin β chain prevents autoimmune diabetes in nonobese diabetic mice. J. Immunol. 167(5), 2950-2955 (2001).
84. Quintana FJ, Carmi P, Cohen IR. DNA vaccination with heat shock protein 60 inhibits cyclophosphamide-accelerated diabetes. J. Immunol. 169(10), 6030-6035 (2002).
85. Quintana FJ, Rotem A, Carmi P, Cohen IR. Vaccination with empty plasmid DNA or CpG oligonucleotide inhibits diabetes in nonobese diabetic mice: modulation of spontaneous 60-kDa heat shock protein autoimmunity. J. Immunol. 165(11), 6148-6155 (2000).
86. Weaver DJ Jr, Liu B, Tisch R. Plasmid DNAs encoding insulin and glutamic acid decarboxylase 65 have distinct effects on the progression of autoimmune diabetes in nonobese diabetic mice. J. Immunol. 167(1), 586-592 (2001).
87. Ruiz PJ, Garren H, Ruiz IU et al. Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: modulation of T cell costimulation. J. Immunol. 162(6), 3336-3341 (1999).
88. Garren H, Ruiz PJ, Watkins TA et al. Combination of gene delivery and DNA vaccination to protect from and reverse Th1 autoimmune disease via deviation to the Th2 pathway. Immunity 15(1), 15-22 (2001).
89. Robinson WH, Fontoura P, Lee BJ et al. Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. Nat. Biotechnol. 21(9), 1033-1039 (2003).
90. Bar-Or A, Vollmer T, Antel J et al. Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled Phase 1/2 trial. Arch. Neurol. 64(10), 1407-1415 (2007).
91. Silver PB, Agarwal RK, Su SB et al. Hydrodynamic vaccination with DNA encoding an immunologically privileged retinal antigen protects from autoimmunity through induction of regulatory T cells. J. Immunol. 179(8), 5146-5158 (2007).
92. Cools N, Ponsaerts P, Van Tendeloo VF, Berneman ZN. Regulatory T cells and human disease. Clin. Dev. Immunol. 2007, 89195 (2007).
93. Jin H, Kang Y, Zheng G et al. Induction of active immune suppression by co-immunization with DNA- and protein-based vaccines. Virology 337(1), 183-191 (2005).
94. Kang Y, Jin H, Zheng G et al. Co-inoculation of DNA and protein vaccines induces antigen-specific T cell suppression. Biochem. Biophys. Res. Commun. 353(4), 1034-1039 (2007).
95. Schif-Zuck S, Wildbaum G, Karin N. Coadministration of plasmid DNA constructs encoding an encephalitogenic determinant and IL-10 elicits regulatory T cell-mediated protective immunity in the central nervous system. J. Immunol. 177(11), 8241-8247 (2006).
96. Eggena MP, Walker LS, Nagabhushanam V, Barron L, Chodos A, Abbas AK. Cooperative roles of CTLA-4 and regu latory T cells in tolerance to an islet cell antigen. J. Exp. Med. 199(12), 1725-1730 (2004).
97. Li AF, Hough J, Henderson D, Escher A. Co-delivery of pro-apoptotic BAX with a DNA vaccine recruits dendritic cells and promotes efficacy of autoimmune diabetes prevention in mice. Vaccine 22(13-14), 1751-1763 (2004).
98. Bárdos T, Czipri M, Vermes C, Zhang J, Mikecz K, Glant TT. Continuous nasal administration of antigen is critical to maintain tolerance in adoptively transferred autoimmune arthritis in SCID mice. Clin. Exp. Immunol. 129(2), 224-231 (2002).
99. Lindquist S. The heat-shock response. Annu. Rev. Biochem. 55, 1151-1191 (1986).
100. Lindquist JA, Jensen ON, Mann M, Hammerling GJ. ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly. EMBO J. 17(8), 2186-2195 (1998).
101. Li Z, Srivastava P. Heat-shock proteins. Curr. Protoc. Immunol. Appendix 1T (2004).
102. Anderton SM, van der Zee R, Prakken B, Noordzij A, van Eden W. Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis. J. Exp. Med. 181(3), 943-952 (1995).
103. Birk OS, Elias D, Weiss AS et al. NOD mouse diabetes: the ubiquitous mouse hsp60 is a β-cell target antigen of autoimmune T cells. J. Autoimmun. 9(2), 159-166 (1996).
104. Birnbaum G, Kotilinek L, Miller SD et al. Heat shock proteins and experimental autoimmune encephalomyelitis. II: environmental infection and extra-neuraxial inflammation alter the course of chronic relapsing encephalomyelitis. J. Neuroimmunol. 90(2), 149-161 (1998).
105. Jorgensen C, Gedon E, Jaquet C, Sany J. Gastric administration of recombinant 65 kDa heat shock protein delays the severity of type II collagen induced arthritis in mice. J. Rheumatol. 25(4), 763-767 (1998).
106. Thompson SJ, Butcher PD, Patel VK et al. Modulation of pristane-induced arthritis by mycobacterial antigens. Autoimmunity 11(1), 35-43 (1991).
107. Hauet-Broere F, Wieten L, Guichelaar T, Berlo S, van der Zee R, Van Eden W. Heat shock proteins induce T cell regulation of chronic inflammation. Ann. Rheum. Dis. 65(Suppl. 3), iii65-iii68 (2006).
108. Quintana FJ, Carmi P, Mor F, Cohen IR. DNA fragments of the human 60-kDa heat shock protein (HSP60) vaccinate against adjuvant arthritis: identification of a regulatory HSP60 peptide. J. Immunol. 171(7), 3533-3541 (2003).
109. Nussbaum G, Zanin-Zhorov A, Quintana F, Lider O, Cohen IR. Peptide p277 of HSP60 signals T cells: inhibition of inflammatory chemotaxis. Int. Immunol. 18(10), 1413-1419 (2006).
110. Willem van Eden. Immunoregulation of autoimmune diseases. Hum. Immunol. 67, 446-453 (2006).
111. Quintana FJ, Carmi P, Mor F, Cohen IR. Inhibition of adjuvant-induced arthritis by DNA vaccination with the 70-kD or the 90-kd human heat-shock protein: immune cross-regulation with the 60-kD heat-shock protein. Arthritis Rheum. 50(11), 3712-3720 (2004).
112. Bandholtz L, Guo Y, Palmberg C et al. Hsp90 binds CpG oligonucleotides directly: implications for Hsp90 as a missing link in CpG signaling and recognition. Cell. Mol. Life Sci. 60, 422-429 (2003).
113. Lukacs KV, Lowrie DB, Stokes RW et al. Tumor cells transfected with a bacterial heat-shock gene lose tumorigenicity and induce protection against tumors. J. Exp. Med. 178, 343-348 (1993).
114. Castelli C, Rivoltini L, Rini F et al. Heat shock proteins: biological functions and clinical application as personalized vaccines for human cancer. Cancer Immunol. Immunother. 53, 227-233 (2004).
115. Jones DB, Coulson AF, Duff GW. Sequence homologies between Hsp60 and autoantigens. Immunol. Today 14(3), 115-118 (1993).
116. Raska M, Weigl E. Heat shock proteins in autoimmune diseases. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech Repub. 149(2), 243-249 (2005).
117. Perschinka H, Mayr M, Millonig G et al. Cross-reactive B-cell epitopes of microbial and human heat shock protein 60/65 in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 23(6), 1060-1065 (2003).
118. Weiner GJ. The immunobiology and clinical potential of immunostimulatory CpG oligodeoxynucleotides. J. Leukoc. Biol. 68(4), 455-463 (2000).
119. Roberts TL, Dunn JA, Terry TD et al. Differences in macrophage activation by bacterial DNA and CpG-containing oligonucleotides. J. Immunol. 175 (6), 3569-3576 (2005).
120. Cornelie S, Poulain-Godefroy O, Lund C et al. Methylated CpG-containing plasmid activates the immune system. Scand. J. Immunol. 59(2), 143-151 (2004).
121. Santos-Junior RR, Sartori A, De Franco M et al. Immunomodulation and protection induced by DNA-hsp65 vaccination in an animal model of arthritis. Hum. Gene Ther. 16(11), 1338-1345 (2005).
122. Vigar ND, Cabrera WH, Araujo LM et al. Pristane-induced arthritis in mice selected for maximal or minimal acute inflammatory reaction. Eur. J. Immunol. 30(2), 431-437 (2000).
123. Krieg AM. From bugs to drugs: therapeutic immunomodulation with oligodeoxynucleotides containing CpG sequences from bacterial DNA. Antisense Nucleic Acid Drug. Dev. 11(3), 181-188 (2001).
124. Roberts TL, Sweet MJ, Hume DA et al. Cutting edge: species-specific TLR9-mediated recognition of CpG and non-CpG phosphorothioate-modified oligonucleotides. J. Immunol. 174(2), 605-608 (2005).
125. Santos-Junior RR, Sartori A, Bonato VL et al. Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression. Clin. Exp. Immunol. 149(3), 570-578 (2007).
126. Pashine A, Valiante NM, Ulmer JB. Targeting the innate immune response with improved vaccine adjuvants. Nat. Med. 11(4 Suppl.), S63-S68 (2005). 127
127. Duramad O, Fearon KL, Chang B et al. Inhibitors of TLR-9 act on multiple cell subsets in mouse and man in vitro and prevent death in vivo from systemic inflammation. J. Immunol. 174, 5193 (2005).
128. Krieg AM, Wu T, Weeratna R et al. Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs. Proc. Natl Acad. Sci. USA 95(21), 12631-12636 (1998).
129. Pisetsky DS, Reich CF. Inhibition of murine macrophage IL-12 production by natural and synthetic DNA. Clin. Immunol. 96(3), 198-204 (2000).
130. Chen Y, Lenert P, Weeratna R et al. Identification of methylated CpG motifs as inhibitors of the immune stimulatory CpG motifs. Gene Ther. 8(13), 1024-1032 (2001).
131. Gursel I, Gursel M, Yamada H, Ishii KJ, Takeshita F, Klinman DM. Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. J. Immunol. 171(3), 1393-1400 (2003).
132. Michaluart P, Abdallah KA, Lima FD et al. Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck. Cancer Gene Ther. 15(10), 676-684 (2008).
133. Victora G, Socorro-Silva A, Volsi EC et al. Immune response to vaccination with DNA-hsp65 in a Phase I clinical trial with head and neck cancer patients. Cancer Gene Ther. (2009) (In Press).
134. + regulatory T cells in vitro. Vaccine 24(23), 5036-5046 (2006).
135. Chang Y, Yap S, Ge X et al. DNA vaccination with an insulin construct and a chimeric protein binding to both CTLA4 and CD40 ameliorates Type 1 diabetes in NOD mice. Gene Ther. 12(23), 1679-1685 (2005).
136. Luo JH, Zhou ZG, Jiang TJ et al. Mechanisms of human glutamic acid decarboxylase 65 DNA vaccine preventing diabetes in non-obese diabetic mice. Zhonghua Yi Xue Za Zhi. 84(21), 1791-1795 (2004).
137. Prud'homme GJ, Chang Y, Li X. Immunoinhibitory DNA vaccine protects against autoimmune diabetes through cDNA encoding a selective CTLA-4 (CD152) ligand. Hum. Gene Ther. 13(3), 395-406 (2002).
138. Onodera S, Ohshima S, Tohyama H et al. A novel DNA vaccine targeting macrophage migration inhibitory factor protects joints from inflammation and destruction in murine models of arthritis. Arthritis Rheum. 56(2), 521-530 (2007).
139. Quintana FJ, Carmi P, Mor F, Cohen IR. Inhibition of adjuvant arthritis by a DNA vaccine encoding human heat shock protein 60. J. Immunol. 169(6), 3422-3428 (2002).
140. Wildbaum G, Westermann J, Maor G, Karin N. A targeted DNA vaccine encoding Fas ligand defines its dual role in the regulation of experimental autoimmune encephalomyelitis. J. Clin. Invest. 106(5), 671-679 (2000).
141. Elkayam O, Yaron M, Caspi D. Safety and efficacy of vaccination against hepatitis B in patients with rheumatoid arthritis. Ann. Rheum. Dis. 61(7), 623-625 (2002).
142. Blank M, Krause I, Wildbaum G, Karin N, Shoenfeld Y. TNF-α DNA vaccination prevents clinical manifestations of experimental antiphospholipid syndrome. Lupus 12(7), 546-549 (2003).
143. Wildbaum G, Karin N. Augmentation of natural immunity to a pro-inflammatory cytokine (TNF-α) by targeted DNA vaccine confers long-lasting resistance to experimental autoimmune encephalomyelitis. Gene Ther. 6(6), 1128-1138 (1999).
144. Ho PP, Fontoura P, Platten M et al. A suppressive oligodeoxynucleotide enhances the efficacy of myelin cocktail/IL-4-tolerizing DNA vaccination and treats autoimmune disease. J. Immunol. 175(9), 6226-6234 (2005).
145. Lobell A, Weissert R, Eltayeb S, Svanholm C, Olsson T, Wigzell H. Presence of CpG DNA and the local cytokine milieu determine the efficacy of suppressive DNA vaccination in experimental autoimmune encephalomyelitis. J. Immunol. 163(9), 4754-4762 (1999).
146. Garren H, Robinson WH, Krasulova E et al. Phase II trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis. Ann. Neurol. 63(5), 611-620 (2008).
147. Garren H. A DNA vaccine for multiple sclerosis. Expert Opin. Biol. Ther. 8(10), 1539-1550 (2008).