DNA vaccines: Immunology, application, and optimization

Annual Review of Immunology

Volumn 18, Issue , 2000, Pages 927-974

  Gurunathan, Sanjay ^a   Klinman, Dennis M ^b   Seder, Robert A ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b CENTER FOR BIOLOGICS EVALUATION AND RESEARCH   (United States)

Author keywords

CpG sequences; Plasmid DNA

Indexed keywords

DNA VACCINE; PROTEIN SUBUNIT; SYNTHETIC DNA;

ANTIBODY RESPONSE; AUTOIMMUNE DISEASE; CANCER RISK; CELLULAR IMMUNITY; DRUG MECHANISM; DRUG SAFETY; HUMAN; HUMAN CELL; HUMAN TISSUE; HUMORAL IMMUNITY; IMMUNOREGULATION; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; VACCINATION;

ANIMALS; CONSUMER PRODUCT SAFETY; GENETIC VECTORS; HUMANS; RATS; VACCINATION; VACCINES, DNA;

EID: 0034046182     PISSN: 07320582     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.immunol.18.1.927     Document Type: Review

References (246)

1. Nicolau C, Le Pape A, Soriano P, Fargette F, Juhel MF. 1983. In vivo expression of rat insulin after intravenous administration of the liposome-entrapped gene for rat insulin I. Proc. Natl. Acad. Sci. USA 80:1068-72
2. Kaneda Y, Iwai K, Uchida T. 1989. Increased expression of DNA cointroduced with nuclear protein in adult rat liver. Science 243:375-78
3. Mannino RJ, Gould-Fogerite S. 1988. Liposome mediated gene transfer. Biotechniques 6:682-90
4. Benvenisty N, Reshef L. 1986. Direct introduction of genes into rats and expression of the genes. Proc. Natl. Acad. Sci. USA 83:9551-55
5. Wu GY, Wu CH. 1988. Receptor-mediated gene delivery and expression in vivo. J. Biol. Chem. 263:14621-24
6. Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Feigner PL. 1990. Direct gene transfer into mouse muscle in vivo. Science 247:1465-68
7. Tang DC, De Vit M, Johnston SA. 1992. Genetic immunization is a simple method for eliciting an immune response. Nature 356:152-54
8. Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, De Witt DM, Friedman A, Hawe LA, Leander KR, Martinez D, Perry HC, Shiver JW, Montgomery DC, Liu MA. 1993. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259:1745-49
9. Robinson HL, Hunt LA, Webster RG. 1993. Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA. Vaccine 11:957-60
10. Robinson HL, Pertmer TM. 1999. DNA vaccines for viral infection: basic studies and applications. Adv. Virus Res. In press
11. Whalen R. http://www.genweb.com/ dnavax/dnavax.html
12. Yamamoto S, Yamamoto T, Shimada S, Kuramoto E, Yano O, Kataoka T, Tokunaga T. 1992. DNA from bacteria, but not from vertebrates, induces interferons, activates natural killer cells and inhibits tumor growth. Microbiol. Immunol. 36:983-97
13. Klinman DM, Yi AK, Beaucage SL, Conover J, Krieg AM. 1996. CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and Interferon γ. Proc. Natl. Acad. Sci. USA 93:2879-83
14. Halpern MD, Kurlander RJ, Pisetsky DS. 1996. Bacterial DNA induces murine interferon-γ production by stimulation of interleukin-12 and tumor necrosis factor-α. Cell Immunol. 167:72-78
15. Sato Y, Roman M, Tighe J, Lee D, Corr M, Nguyen MD, Silverman GJ, Lotz M, Carson DA, Raz E. 1996. Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science 273:352-54
16. Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM. 1995. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374:546-49
17. Cardon LR, Burge C, Clayton DA, Karlin S. 1994. Pervasive CpG suppression in animal mitochondrial genomes. Proc. Natl. Acad. Sci. USA 91:3799-803
18. Razin A, Friedman J. 1981. DNA methylation and its possible biological roles. Prog. Nucl. Acid Res. Mol. Biol 25:33-52
19. Stacey KJ, Sweet MJ, Hume DA. 1996. Macrophages ingest and are activated by bacterial DNA. J. Immunol. 157:2116-22
20. Jakob T, Walker PS, Krieg AM, Udey MC, Vogel JC. 1998. Activation of cutaneous dendritic cells by CpG-containing oligodeoxynucleotides: a role for dendritic cells in the augmentation of Th1 responses by immunostimulatory DNA. J. Immunol. 161:3042-49
21. Cowdery JS, Chace JH, Yi AK, Krieg AM. 1996. Bacterial DNA induces NK cells to produce IFN-γ in vivo and increases the toxicity of lipopolysaccharides. J. Immunol. 156:4570-75
22. Bendigs S, Salzer U, Lipford GB, Wagner H, Heeg K. 1999. CpG-oligodeoxynucleotides co-stimulate primary T cells in the absence of antigen-presenting cells. Eur. J. Immunol. 29:1209-18
23. Corr M, Lee DJ, Carson DA, Tighe H. 1996. Gene vaccination with naked plasmid DNA: mechanism of CTL priming. J. Exp. Med. 184:1555-60
24. Iwasaki A, Torres CA, Ohashi PS, Robinson HL, Barber BH. 1997. The dominant role of bone marrow-derived cells in CTL induction following plasmid DNA immunization at different sites. J. Immunol. 159:11-14
25. Doe B, Selby M, Barnett S, Baenziger J, Walker CM. 1996. Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells. Proc. Natl. Acad. Sci. USA 93:8578-83
26. Casares S, Inaba K, Brumeanu TD, Steinman RM, Bona CA. 1997. Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class Π-restricted viral epitope. J. Exp. Med. 186:1481-86
27. + T cells after gene gun immunization. J. Exp. Med. 188:1075-82
28. Akbari O, Panjwani N, Garcia S, Tascon R, Lowrie D, Stockinger B. 1999. DNA vaccination: transfection and activation of dendritic cells as key events for immunity. J. Exp. Med. 189:169-78
29. Condon C, Watkins SC, Celluzzi CM, Thompson K, Falo LD Jr. 1996. DNA-based immunization by in vivo transfection of dendritic cells. Nat. Med. 2:1122-28
30. Ulmer JB, Deck RR, Dewitt CM, Donnhly JI, Liu MA. 1996. Generation of MHC class I-restricted cytotoxic T lymphocytes by expression of a viral protein in muscle cells: antigen presentation by non-muscle cells. Immunology 89:59-67
31. Agadjanyan MG, Kim JJ, Trivedi N, Wilson DM, Monzavi-Karbassi B, Morrison LD, Nottingham LK, Dentchev T, Tsai A, Dang K, Chalian AA, Maldonado MA, Williams WV, Weiner DB. 1999. CD86 (B7-2) can function to drive MHC-restricted antigen-specific CTL responses in vivo. J. Immunol. 162: 3417-27
32. Iwasaki A, Stiernholm BJ, Chan AK, Berinstein NL, Barber BH. 1997. Enhanced CTL responses mediated by plasmid DNA immunogens encoding costimulatory molecules and cytokines. J. Immunol. 158:4591-601
33. Torres CA, Iwasaki A, Barber BH, Robinson HL. 1997. Differential dependence on target site tissue for gene gun and intramuscular DNA immunizations. J. Immunol. 158:4529-32
34. Yang NS, Burkholder J, Roberts B, Martinell B, McCabe D. 1990. In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc. Natl. Acad. Sci. USA 87:9568-72
35. Raz E, Carson DA, Parker SE, Parr TB, Abai AM, Aichinger G, Gromkowski SH, Singh M, Lew D, Yankauckas MA, Baird SM, Rhodes GH. 1994. Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc. Natl. Acad. Sci. USA 91:9519-23
36. Klinman DM, Sechler JM, Conover J, Gu M, Rosenberg AS. 1998. Contribution of cells at the site of DNA vaccination to the generation of antigen-specific immunity and memory. J. Immunol. 160:2388-92
37. Wraith DC, Vessey AE, Askonas BA. 1987. Purified influenza virus nucleoprotein protects mice from lethal infection. J. Gen. Virol. 68:433-40
38. Staerz UD, Karasuyama H, Garner AM. 1987. Cytotoxic T lymphocytes against a soluble protein. Nature 329:449-51
39. Harding CV, Song R. 1994. Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules. J. Immunol. 153:4925-33
40. Falo LD Jr, Kovacsovics-Akowski M, Thompson K, Rock KL. 1995. Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity. Nat. Med. 1:649-53
41. Udono H, Srivastava PK. 1993. Heat shock protein 70-associated peptides elicit specific cancer immunity. J. Exp. Med. 178:1391-96
42. Fu TM, Ulmer JB, Caulfield MJ, Deck RR, Friedman A, Wang S, Liu X, Donnelly JJ, Liu MA. 1997. Priming of cytotoxic T lymphocytes by DNA vaccines: requirement for professional antigen presenting cells and evidence for antigen transfer from myocytes. Mol. Med. 3:362-71
43. Albert ML, Sauter B, Bhardwaj N. 1998. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86-89
44. Albert ML, Pearce SF, Francisco LM, Sauter B, Roy P, Silverstein RL, Bhardwaj N. 1998. Immature dendritic cells phagocytose apoptotic cells via αVβ5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J. Exp. Med. 188:1359-68
45. Banchereau J, Bazan F, Blanchard D, Briere F, Galizzi LP, van Kooten C, Liu YJ, Rousset F, Saeland S. 1994. The CD40 antigen and its ligand. Annu. Rev. Immimol. 12:881-922
46. + T-helper and a T-killer cell. Nature 393:474-78
47. Bennett SRM, Carbone FR, Karamalis F, Flavell RA, Miller J, Heath WR. 1998. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 393:478-80
48. Schoenberger SP, Toes REM, van der Voort EIH, Offringa R, Melief CJM. 1998. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393:480-83
49. + T cells. Annu. Rev. Immunol. 12:635-73
50. O'Garra A. 1998. Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8:275-83
51. Wans ME, Tsou C, Erdman DD, Zaki SR, Anderson LJ. 1996. Respiratory synctial virus infection in BALB/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern. J. Virol. 70:2852-60
52. Li X, Sambhara S, Li CX, Ewasyshyn M, Parrington M, Caterini J, James O, Cates G, Du RP, Klein M. 1998. Protection against respiratory syncytial virus infection by DNA immunization. J. Exp. Med. 188:681-88
53. Roman M, Martin-Orozco E, Goodman JS, Nguyen MD, Sato Y, Ronaghy A, Kornbluth RS, Richman DD, Carson DA, Raz E. 1997. Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat. Med. 3:849-54
54. Pertmer TM, Roberts TR, Haynes JR. 1996. 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. 70:6119-25
55. Feltquate DM, Heaney S, Webster RG, Robinson HL. 1997. Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol. 158:2278-84
56. Suss G, Shortman K. 1996. A subclass of dendritic cells kills CD4 T cells via Fas/Fas ligand-induced apoptosis. J. Exp. Med. 183:1789-96
57. Pulendran B, Smith JL, Caspary G, Brasel K, Pettit D, Maraskovsky E, Maliszewski CR. 1999. Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Proc. Natl. Acad. Sci. USA 96:1036-41
58. + dendritic cells generate an immune response after subcutaneous injection without homing to the draining lymph node. J. Exp. Med. 189:593-98
59. Rissoan MC, Soumelis V, Kadowaki N, Grouard G, Briere F, de Waal Malefyt R, Liu YJ. 1999. Reciprocal control of T helper cell and dendritic cell differentiation. Science 283:1183-86
60. - subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J. Exp. Med. 189:587-92
61. Boyle JS, Koniaras C, Lew AM. 1997. Influence of cellular location of expressed antigen on the efficacy of DNA vaccination: cytotoxic T lymphocyte and antibody responses are suboptimal when antigen is cytoplasmic after intramuscular DNA immunization. Int. Immunol. 9:1897-906
62. Haddad D, Liljeqvist S, Stahl S, Andersson I, Perlmann P, Berzins K, Ahlborg N. 1997. Comparative study of DNA-based immunization vectors: effect of secretion signals on the antibody responses in mice. FEMS Immunol. Med. Microbiol. 18:193-202
63. Zimmermann S, Egeter O, Hausmann S, Lipford GB, Rocken M, Wagner H, Heeg K. 1998. CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis. J. Immunol. 160:3627-30
64. Raz E, Tighe H, Sato Y, Corr M, Dudler JA, Roman M, Swain SL, Spiegelberg HL, Carson DA. 1996. Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proc. Natl. Acad. Sci. USA 93:5141-45
65. Hsu CH, Chua KY, Tao MH, Lai YL, Wu HD, Huang SK, Hsieh KH. 1996. Immunoprophylaxis of allergen-induced immunoglobulin E synthesis and airway hyperresponsiveness in vivo by genetic immunization. Nat. Med. 2:540-44
66. Segal BM, Klinman DM, Shevach EM. 1997. Microbial products induce autoimmune disease by an IL-12-dependent pathway. J. Immunol. 158:5087-90
67. Waisman A, Ruiz PJ, Hirschberg DL, Gelman A, Oksenberg JR, Brocke S, Mor F, Cohen IR, Steinman L. 1996. Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity. Nat. Med. 2:899-905
68. Martins LP, Lau LL, Asano MS, Ahmed R. 1995. DNA vaccination against persistent viral infection. J. Virol. 69:2574-82
69. Yokoyama M, Zhang J, Whitton JL. 1995. DNA immunization confers protection against lethal lymphocytic choriomeningitis virus infection. J. Virol. 69:2684-88
70. Zarozinski CC, Fynan EF, Selin LK, Robinson HL, Welsh RM. 1995. Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein. J. Immunol. 154:4010-17
71. + T cell responses to dominant and subdominant epitopes and protective immunity to Sendai virus infection by DNA vaccination. J. Immunol. 160:2425-32
72. Fu TM, Friedman A, Ulmer JB, Liu MA, Donnelly JJ. 1997. Protective cellular immunity: cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA immunization. J. Virol. 71:2715-21
73. Deck RR, DeWitt CM, Donnelly JJ, Liu MA, Ulmer JB. 1997. Characterization of humoral immune responses induced by an influenza hemagglutinin DNA vaccine. Vaccine 15:71-78
74. Robinson HL, Boyle CA, Feltquate DM, Morin MJ, Santoro JC, Webster RG. 1997. DNA immunization for influenza virus: studies using hemagglutinin-and nucleoprotein-expressing DNAs. J. Infect. Dis. 176:S50-55 (Suppl)
75. Boyle CM, Morin M, Webster RG, Robinson HL. 1996. Role of different lymphoid tissues in the initiation and maintenance of DNA-raised antibody responses to the influenza virus H1 glycoprotein. J. Virol. 70:9074-78
76. Kang Y, Calvo PA, Daly TM, Long CA. 1998. Comparison of humoral immune responses elicited by DNA and protein vaccines based on merozoite surface protein-1 from Plasmodium yoelii, a rodent malaria parasite. J. Immunol. 161:4211-19
77. Boyle JS, Silva A, Brady JL, Lew AM. 1997. DNA immunization: induction of higher avidity antibody and effect of route on T-cell cytotoxicity. Proc. Natl. Acad. Sci. USA 94:14626-31
78. Peet NM, McKeating JA, Ramos B, Klonisch T, De Souza JB, Delves PJ, Lund T. 1997. Comparison of nucleic acid and protein immunization for induction of antibodies specific for HIV-1 gp120. Clin. Exp. Immunol 109:226-32
79. Donnelly JJ, Martinez D, Jansen KU, Ellis RW, Montgomery DL, Liu MA. 1996. Protection against papillomavirus with a polynucleotide vaccine. J. Infect. Dis. 173:314-20
80. Gurunathan S, Prussin C, Sacks DL, Seder RA. 1998. Vaccine requirements for sustained cellular immunity to an intracellular parasitic infection. Nat. Med. 4:1409-15
81. Davis HL, Schirmbeck R, Reimann J, Whalen RG. 1995. DNA-mediated immunization in mice induces a potent MHC class I-restricted cytotoxic T lymphocyte response to the hepatitis B envelope protein. Hum. Gene Ther. 6:1447-56
82. Tough DF, Borrow P, Sprent J. 1996. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272:1947-50
83. Sun S, Zhang X, Tough DF, Sprent J. 1998. Type I interferon-mediated stimulation of T cells by CpG DNA. J. Exp. Med. 188:2335-42
84. Wolff JA, Ludtke JJ, Acsadi G, Williams P, Jani A. 1992. Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. Mol. Genet. 1:363-69
85. Manthorpe M, Cornefert-Jensen F, Hartikka J, Feigner J, Rundell A, Margalith M, Dwarki V. 1993. Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Hum. Gene Ther. 4:419-31
86. Cheng L, Ziegelhoffer PR, Yang NS. 1993. In vivo promoter activity and transgene expression in mammalian somatic tissues evaluated by using particle bombardment. Proc. Natl. Acad. Sci. USA 90:4455-59
87. Chapman BS, Thayer RM, Vincent KA, Haigwood NL. 1991. Effect of intron A from human cytomegalovirus (Towne) immediate-early gene on heterologous expression in mammalian cells. Nucl. Acids Res. 19:3979-86
88. Norman JA, Hobart P, Manthorpe M, Feigner P, Wheeler C. 1997. Development of improved vectors for DNA-based immunization and other gene therapy applications. Vaccine 15:801-3
89. Wild J, Gruner B, Metzger K, Kuhrober A, Pudollek HP, Hauser H, Schirmbeck R, Reimann J. 1998. Polyvalent vaccination against hepatitis B surface and core antigen using a dicistronic expression plasmid. Vaccine 16:353-60
90. Lewin B, ed. 1994. Genes V. Oxford Univ. Press/Cell. 5th ed.
91. Uchijima M, Yoshida A, Nagata T, Koide Y. 1998. Optimization of codon usage of plasmid DNA vaccine is required for the effective MHC class I-restricted T cell responses against an intracellular bacterium. J. Immunol. 161:5594-99
92. Andre S, Seed B, Eberle J, Schraut W, Bultmann A, Haas J. 1998. Increased immune response elicited by DNA vaccination with a synthetic gp120 sequence with optimized codon usage. J. Virol. 72:1497-503
93. Vinner L, Nielsen HV, Bryder K, Corbet S, Nielsen C, Fomsgaard A. 1999. Gene gun DNA vaccination with Rev-independent synthetic HW-1 gp160 envelope gene using mammalian codons. Vaccine 17:2166-75
94. Lewis PJ, Cox GJ, van Drunen Littel-van den Hurk S, Babiuk LA. 1997. Polynucleotide vaccines in animals: enhancing and modulating responses. Vaccine 15:861-64
95. Inchauspe G, Vitvitski L, Major ME, Jung G, Spengler U, Maisonnas M, Trepo C. 1997. Plasmid DNA expressing a secreted or a nonsecreted form of hepatitis C virus nucleocapsid: comparative studies of antibody and T-helper responses following genetic immunization. DNA Cell Biol. 16:185-95
96. Rice J, King CA, Spellerberg MB, Fairweather N, Stevenson FK. 1999. Manipulation of pathogen-derived genes to influence antigen presentation via DNA vaccines. Vaccine 17:3030-38
97. Wu Y, Kipps TJ. 1997. Deoxyribonucleic acid vaccines encoding antigens with rapid proteasome-dependent degradation are highly efficient inducers of cytolytic T lymphocytes. J. Immunol 159:6037-43
98. Tobery TW, Siliciano RF. 1997. Targeting of HFV-1 antigens for rapid intracellular degradation enhances cytotoxic T lymphocyte (CTL) recognition and the induction of de novo CTL responses in vivo after immunization. J. Exp. Med. 185:909-20
99. Rodriguez F, Zhang J, Whitton JL. 1997. DNA immunization: ubiquitination of a viral protein enhances cytotoxic T-lymphocyte induction and antiviral protection but abrogates antibody induction. J. Virol. 71:8497-503
100. Whitton JL, Rodriguez F, Zhang J, Hassett DE. 1999. DNA immunization: mechanistic studies. Vaccine 17:1612-19
101. Ciernik IF, Berzofsky JA, Carbone DP. 1996. Induction of cytotoxic T-lymphocytes and antitumor immunity with DNA vaccines expressing single T-cell epitopes. J. Immunol. 156:2369-75
102. Iwasaki A, Dela Cruz CS, Young AR, Barber BH. 1999. Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization. Vaccine 17:2081-88
103. Yu Z, Karem KL, Kanangat S, Manickan E, Rouse BT. 1998. Protection by minigenes: a novel approach of DNA vaccines. Vaccine 16:1660-67
104. Hanke T, Schneider J, Gilbert SC, Hill AV, McMichael A. 1998. DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum: immunogenicity in mice. Vaccine 16:426-35
105. Thomson SA, Sherritt MA, Medveczky J, Elliott SL, Moss DJ, Fernando JG, Brown LE, Suhrbier A. 1998. Delivery of multiple CDS cytotoxic T cell epitopes by DNA vaccination. J. Immunol. 160:1717-23
106. Suhrbier A. 1997. Multi-epitope DNA vaccines. Immunol. Cell Biol. 75:402-8
107. Wang R, Doolan DL, Charoenvit Y, Hedstrom RC, Gardner NJ, Hobart P, Tine J, Sedegah M, Fallarme V, Sacci JB Jr, Kaur M, Klinman DM, Hoffman SL, Weiss WR. 1998. Simultaneous induction of multiple antigen-specific cytotoxic T lymphocytes in nonhuman primates by immunization with a mixture of four Plasmodium falciparum DNA plasmids. Infect. Immun. 66:4193-202
108. Shi YP, Hasnain SE, Sacci JB, Holloway BP, Fujioka H, Kumar N, Wohlhueter R, Hoffman SL, Collins WE, Lal AA. 1999. Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine. Proc. Natl. Acad. Sci. USA 96:1615-20
109. Maecker HT, Umetsu DT, DeKruyff RH, Levy S. 1998. Cytotoxic T cell responses to DNA vaccination: dependence on antigen presentation via class II MHC. J. Immunol. 161:6532-36
110. Klinman DM, Yamshchikov G, Ishigatsubo Y. 1997. Contribution of CpG motifs to the immunogenicity of DNA vaccines. J. Immunol. 158:3635-39
111. Brazolot Millan CL, Weeratna R, Krieg AM, Siegrist CA, Davis HL. 1998. CpG DNA can induce strong Th 1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice. Proc. Natl. Acad. Sci. USA 95:15553-58
112. Davis HL, Weeranta R, Waldschmidt TJ, Tygrett L, Schorr J, Krieg AM. 1998. CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. J. Immunol. 160:870-76
113. Klinman DM. 1998. Therapeutic applications of CpG-containing oligodeoxynucleotides. Antisense Nucl. Acid Drug Dev. 8:181-84
114. Klinman DM, Barnhart KM, Conover J. 1999. CpG motifs as immune adjuvants. Vaccine 17:19-25
115. Krieg AM, Wu T, Weeratna R, Efler SM, Love-Homan L, Yang L, Yi AK, Short D, Davis HL. 1998. Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs. Proc. Natl. Acad. Sci. USA 95:12631-36
116. Liang H, Nishioka Y, Reich CF, Pisetsky DS, Lipsky PE. 1996. Activation of human B cells by phosphorothioate oligodeoxynucleotides. J. Clin. Invest. 98: 1119-29
117. Ballas ZK, Rasmussen WL, Krieg AM. 1996. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J. Immunol. 157:1840-45
118. Hacker H, Mischak H, Miethke T, Liptay S, Schmid R, Sparwasser T, Heeg K, Lipford GB, Wagner H. 1998. CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J. 17:6230-40
119. Richmond JF, Mustafa F, Lu S, Santoro JC, Weng J, O'Connell M, Fenyo EM, Hurwitz JL, Montefiori DC, Robinson HL. 1997. Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting. Virology 230:265-74
120. Richmond JF, Lu S, Santoro JC, Weng J, Hu SL, Montefiori DC, Robinson HL. 1998. Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 Env antibody elicited by DNA priming and protein boosting. J. Virol. 72:9092-100
121. Mustafa F, Richmond JF, Fernandez-Larsson R, Lu S, Fredriksson R, Fenyo EM, O'Connell M, Johnson E, Weng J, Santoro JC, Robinson HL. 1997. HIV-1 Env glycoproteins from two series of primary isolates: replication phenotype and immunogenicity. Virology 229:269-78
122. Fuller DH, Murphey-Corb M, Clements J, Barnett S, Haynes JR. 1996. Induction of immunodeficiency virus-specific immune responses in rhesus monkeys following gene gun-mediated DNA vaccination. J. Med. Primatol. 25:236-41
123. Fuller DH, Haynes JR. 1994. A qualitative progression in HIV type 1 glycoprotein 120-specific cytotoxic cellular and humoral immune responses in mice receiving a DNA-based glycoprotein 120 vaccine. AIDS Res. Hum. Retrovir. 10:1433-41
124. Lu S, Wyatt R, Richmond JF, Mustafa F, Wang S, Weng J, Montefiori DC, Sodroski J, Robinson HL. 1998. Immunogenicity of DNA vaccines expressing human immunodeficiency virus type 1 envelope glycoprotein with and without deletions in the V1/2 and V3 regions. AIDS Res. Hum. Retrovir. 14:151-55
125. Lu S, Manson K, Wyand M, Robinson HL. 1997. SIV DNA vaccine trial in macaques: post-challenge necropsy in vaccine and control groups. Vaccine 15:920-23
126. Okuda K, Xin KO, Tsuji T, Bukawa H, Tanaka S, Koff WC, Tani K, Honma K, Kawamoto S, Hamajima K, Fukushima J. 1997. DNA vaccination followed by macromolecular multicomponent peptide vaccination against HIV-1 induces strong antigen-specific immunity. Vaccine 15:1049-56
127. Barnett SW, Rajasekar S, Legg H, Doe B, Fuller DH, Haynes JR, Walker CM, Steimer KS. 1997. Vaccination with HIV-1 gp120 DNA induces immune responses that are boosted by a recombinant gp120 protein subunit. Vaccine 15:869-73
128. Letvin NL, Montefiori DC, Yasutomi Y, Perry HC, Davies ME, Lekutis C, Alroy M, Freed DC, Lord CI, Handt LK, Liu MA, Shiver JW. 1997. Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination. Proc. Natl. Acad. Sci. USA 94:9378-83
129. Fuller DH, Corb MM, Barnett S, Steimer K, Haynes JR. 1997. Enhancement of immunodeficiency virus-specific immune responses in DNA-immunized rhesus macaques. Vaccine 15:924-26
130. Hanke T, Blanchard TJ, Schneider J, Hannan CM, Becker M, Gilbert SC, Hill AV, Smith GL, McMichael A. 1998. Enhancement of MHC class I-restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime. Vaccine 16:439-45
131. Sedegah M, Jones TR, Kaur M, Hedstrom R, Hobart P, Tine JA, Hoffman SL. 1998. Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine. Proc. Natl. Acad. Sci. USA 95:7648-53
132. + T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nat. Med. 4:397-402
133. Kent SJ, Zhao A, Best SJ, Chandler JD, Boyle DB, Ramshaw IA. 1998. Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. J. Virol. 72:10180-88
134. Robinson HL, Montefiori DC, Johnson RP, Manson KH, Kalish ML, Lifson JD, Rizvi TA, Lu S, Hu SL, Mazzara GP, Panicali DL, Herndon JG, Glickman R, Candido MA, Lydy SL, Wyand MS, McClure HM. 1999. Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations. Nat. Med. 5:526-34
135. Fynan EF, Webster RG, Fuller DH, Haynes JR, Santoro JC, Robinson HL. 1993. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Natl Acad. Sci. USA 90:11478-82
136. Jones DH, Corns S, McDonald S, Clegg JC, Farrar GH. 1997. Poly(DL-lactide-co-glycolide)-encapsulated plasmid DNA elicits systemic and mucosal antibody responses to encoded protein after oral administration. Vaccine 15:814-17
137. Chen SC, Jones DH, Fynan EF, Farrar GH, Clegg JC, Greenberg HB, Herrmann JE. 1998. Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles. J. Viral. 72:5757-61
138. Herrmann JE, Chen SC, Jones DH, Tinsley-Bown A, Fynan EF, Greenberg HB, Farrar GH. 1999. Immune responses and protection obtained by oral immunization with rotavirus VP4 and VP7 DNA vaccines encapsulated in microparticles. Virology 259:148-53
139. Roy K, Mao HQ, Huang SK, Leong KW. 1999. Oral gene delivery with chitosan-DNA nanoparticles generates immunologie protection in a murine model of peanut allergy. Nat. Med. 5:387-91
140. Klavinskis LS, Gao L, Barnfield C, Lehner T, Parker S. 1997. Mucosal immunization with DNA-liposome complexes. Vaccine 15:818-20
141. Ban EM, van Ginkel FW, Simecka JW, Kiyono H, Robinson HL, McGhee JR. 1997. Mucosal immunization with DNA encoding influenza hemagglutinin. Vaccine 15:811-13
142. Kuklin N, Daheshia M, Karem K, Manickan E, Rouse BT. 1997. Induction of mucosal immunity against herpes simplex virus by plasmid DNA immunization. J. Virol 71:3138-45
143. Sasaki S, Hamajima K, Fukushima J, Ihata A, Ishii N, Gorai I, Hirahara F, Mohri H, Okuda K. 1998. Comparison of intranasal and intramuscular immunization against human immunodeficiency virus type 1 with a DNA-monophosphoryl lipid A adjuvant vaccine. Infect. Immun. 66:823-26
144. Sasaki S, Sumino K, Hamajima K, Fukushima J, Ishii N, Kawamoto S, Mohri H, Kensil CR, Okuda K. 1998. Induction of systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 saponin adjuvant via intramuscular and intranasal routes. J. Virol. 72:4931-39
145. Sasaki S, Fukushima J, Hamajima K, Ishii N, Tsuji T, Xin KQ, Mohri H, Okuda K. 1998. Adjuvant effect of Ubenimex on a DNA vaccine for HIV-1. Clin. Exp. Immunol. 111:30-35
146. Wang B, Dang K, Agadjanyan MG, Srikantan V, Li F, Ugen KE, Boyer J, Merva M, Williams WV, Weiner DB. 1997. Mucosal immunization with a DNA vaccine induces immune responses against HIV-1 at a mucosal site. Vaccine 15:821-25
147. Livingston JB, Lu S, Robinson H, Anderson DJ. 1998. Immunization of the female genital tract with a DNA-based vaccine. Infect. Immun. 66:322-29
148. Shi Z, Curiel DT, Tang DC. 1999. DNA-based non-invasive vaccination onto the skin. Vaccine 17:2136-41
149. Davis HL, Jasmin BJ. 1993. Direct gene transfer into mouse diaphragm. FEBS Lett. 333:146-50
150. Davis HL, Michel ML, Mancini M, Schleef M, Whalen RG. 1994. Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen. Vaccine 12:1503-9
151. Wang R, Doolan DL, Le TP, Hedstrom RC, Coonan KM, Charoenvit Y, Jones TR, Hobart P, Margalith M, Ng J, Weiss WR, Sedegah M, de Taisne C, Norman JA, Hoffman SL. 1998. Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science 282:476-80
152. Leitner WW, Seguin MC, Ballou WR, Seitz JP, Schultz AM, Sheehy MJ, Lyon JA. 1997. Immune responses induced by intramuscular or gene gun injection of protective deoxyribonucleic acid vaccines that express the circumsporozoite protein from Plasmodium berghei malaria parasites. J. Immunol. 159:6112-19
153. Tsan MF, White JE, Shepard B. 1995. Lung-specific direct in vivo gene transfer with recombinant plasmid DNA. Am. J. Physiol. 268:L1052-56
154. Meyer KB, Thompson MM, Levy MY, Barron LG, Szoka FC Jr. 1995. Intratracheal gene delivery to the mouse airway: characterization of plasmid DNA expression and pharmacokinetics. Gene Ther. 2:450-60
155. Stribling R, Brunette E, Liggitt D, Gaensler K, Debs R. 1992. Aerosol gene delivery in vivo. Proc. Natl. Acad. Sci. USA 89:11277-81
156. McDonald RJ, Liggitt HD, Roche L, Nguyen HT, Pearlman R, Raabe OG, Bussey LB, German CM. 1998. Aerosol delivery of lipid:DNA complexes to lungs of rhesus monkeys. Pharm. Res. 15:671-79
157. Okada E, Sasaki S, Ishii N, Aoki I, Yasuda T, Nishioka K, Fukushima J, Miyazaki J, Wahren B, Okuda K. 1997. Intranasal immunization of a DNA vaccine with IL-12-and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens. J. Immunol. 159:3638-47
158. Kuklin NA, Daheshia M, Chun S, Rouse BT. 1998. Immunomodulation by mucosal gene transfer using TGF-β DNA. J. Clin. Invest. 102:438-44
159. Kawabata K, Takakura Y, Hashida M. 1995. The fate of plasmid DNA after intravenous injection in mice: involvement of scavenger receptors in its hepatic uptake. Pharm. Res. 12:825-30
160. Lew D, Parker S, Latimer T, Abai A, Kuwahara-Rundell A, Doh S, Yang Z-Y, Gromkowski S, Nabel G, Manthrope M, Norman J. 1995. Cancer gene therapy using plasmid DNA: pharmacokinectic study of DNA following injection in mice. Hum. Gene Ther. 6:553-64
161. Williams RS, Johnston SA, Riedy M, De Vit MJ, McElligott SG, Sanford JC. 1991. Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles. Proc. Natl. Acad. Sci. USA 88:2726-30
162. Gregoriadis G, Saffie R, de Souza JB. 1997. Liposome-mediated DNA vaccination. FEBS Lett. 402:107-10
163. Gould-Fogerite S, Kheiri MT, Zang F, Wang Z, Scolpino AJ, Feketeova E, Canki M, Mannino RJ. 1998. Targetting immune response induction with cochleate and liposomal-based vaccines. Adv. Drug Del. Rev. 32:273-87
164. Mannino RJ, Gould-Fogerite S. 1997. Antigen cochleate preparations for oral and systemic vaccination. In New Generation Vaccines, eds. ML Levine, GC Woodrow, JB Kaper, GS Cobon. New York: Marcel Dekker. 2nd ed.
165. Gould-Fogerite S, Mannino RJ. 1996. Mucosal and systemic immunization using cochleate and liposome vaccines. J. Liposome Res. 2:357-79
166. Sizemore DR, Branstrom AA, Sadoff JC. 1995. Attenuated Shigella as a DNA delivery vehicle for DNA-mediated immunization. Science 270:299-302
167. Sizemore DR, Branstrom AA, Sadoff JC. 1997. Attenuated bacteria as a DNA delivery vehicle for DNA-mediated immunization. Vaccine 15:804-7
168. Darji A, Guzman CA, Gerstel B, Wachholz P, Timmis KN, Wehland J, Chakraborty T, Weiss S. 1997. Oral somatic transgene vaccination using attenuated S. typhimurium. Cell 91:765-75
169. Paglia P, Medina E, Arioli I, Guzman CA, Colombo MP. 1998. Gene transfer in dendritic cells, induced by oral DNA vaccination with Salmonella typhimurium, results in protective immunity against a murine fibrosarcoma. Blood 92:3172-76
170. Dietrich G, Bubert A, Gentschev I, Sokolovic Z, Simm A, Catic A, Kaufmann SH, Hess J, Szalay AA, Goebel W. 1998. Delivery of antigen-encoding plasmid DNA into the cytosol of macrophages by attenuated suicide Listeria monocytogenes. Nat. Biotechnol. 16:181-85
171. Fennelly GJ, Khan SA, Abadi MA, Wild TF, Bloom BR. 1999. Mucosal DNA vaccine immunization against measles with a highly attenuated Shigella flexneri vector. J. Immimol. 162:1603-10
172. Courvalin P, Goussard S, Grillot-Courvalin C. 1995. Gene transfer from bacteria to mammalian cells. C.R. Acad. Sci. III 318:1207-12
173. Tubulekas I, Berglund P, Fleeton M, Liljestrom P. 1997. Alphavirus expression vectors and their use as recombinant vaccines: a minireview. Gene 190:191-95
174. Driver DA, Latham EM, Polo JM, Belli BA, Banks TA, Chada S, Brumm D, Chang SMW, Mento SJ, Jolly DJ, Dubensky TW. 1995. Layered amplification of gene expression with a DNA gene delivery system. Ann. NY Acad. Sci. 772:261-64
175. Dubensky TW Jr, Driver DA, Polo JM, Belli BA, Latham EM, Ibanez CE, Chada S, Brumm D, Banks TA, Mento SJ, Jolly DJ, Chang SM. 1996. Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer. J. Virol. 70:508-19
176. Herweijer H, Latendresse JS, Williams P, Zhang G, Danko I, Schlesinger S, Wolff JA. 1995. A plasmid-based self-amplifying Sindbis virus vector. Hum. Gene Ther. 6:1161-67
177. Berglund P, Smerdou C, Fleeton MN, Tubulekas I, Liljestrom P. 1998. Enhancing immune responses using suicidal DNA vaccines. Nat. Biotechnol. 16:562-65
178. Hariharan MJ, Driver DA, Townsend K, Brumm D, Polo JM, Belli BA, Catton DJ, Hsu D, Mittelstaedt D, McCormack JE, Karavodin L, Dubensky TW Jr, Chang SM, Banks TA. 1998. DNA immunization against herpes simplex virus: enhanced efficacy using a Sindbis virus-based vector. J. Virol. 72:950-58
179. Gerloni M, Baliou WR, Billetta R, Zanetti M. 1997. Immunity to Plasmodium falciparum malaria sporozoites by somatic transgene immunization. Nat. Biotechnol. 15:876-81
180. Xiong S, Gerloni M, Zanetti M. 1997. Engineering vaccines with heterologous B and T cell epitopes using immunoglobulin genes. Nat. Biotechnol. 15:882-86
181. Klinman DM, Takeno M, Ichino M, Gu M, Yamshchikov G, Mor G, Conover J. 1997. DNA vaccines: safety and efficacy issues. Springer Semin, Immunopathol, 19:245-56
182. Martin T, Parker SE, Hedstrom R, Le T, Hoffman SL, Norman J, Hobart P, Lew D. 1999. Plasmid DNA malaria vaccine: the potential for genomic integration after intramuscular injection. Hum. Gene Ther. 10:759-68
183. Gilkeson GS, Ruiz P, Howell D, Lefkowith JB, Pisetsky DS. 1993. Induction of immune-mediated glomerulonephritis in normal mice immunized with bacterial DNA. Clin, Immunol. Immunopathol. 68:283-92
184. Gilkeson GS, Pippen AM, Pisetsky DS. 1995. Induction of cross-reactive anti-dsDNA antibodies in preautoimmune NZB/NZW mice by immunization with bacterial DNA. J. Clin. Invest. 95:1398-402
185. Steinberg AD, Krieg AM, Gourley MF, Klinman DM. 1990. Theoretical and experimental approaches to generalized autoimmunity. Immunol. Rev. 118:129-63
186. Klinman DM. 1990. Polyclonal B cell activation in lupus-prone mice precedes and predicts the development of autoimmune disease. J. Clin. Invest. 86: 1249-54
187. Klinman DM, Steinberg AD. 1987. Systemic autoimmune disease arises from polyclonal B cell activation. J. Exp. Med. 165:1755-60
188. Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR. 1991. Elevated levels of endogenous IL-6 in systemic lupus erythematosus: a putative role in pathogenesis. J. Immunol. 147:117-23
189. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. 1992. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356: 314-17
190. Krieg AM. 1995. CpG DNA: a pathogenic factor in systemic lupus erythematosus? J. Clin. Immunol. 15:284-92
191. Yi AK, Hornbeck P, Lafrenz DE, Krieg AM. 1996. 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. 157:4918-25
192. Katsumi A, Emi N, Abe A, Hasegawa Y, Ito M, Saito H. 1994. Humoral and cellular immunity to an encoded protein induced by direct DNA injection. Hum.Gene Ther. 5:1335-39
193. Mor G, Singla M, Steinberg AD, Hoffman SL, Okuda K, Klinman DM. 1997. Do DNA vaccines induce autoimmune disease? Hum. Gene Ther. 8:293-300
194. Xiang ZQ, Spitalnik SL, Cheng J, Erikson J, Wojczyk B, Ertl HC. 1995. Immune responses to nucleic acid vaccines to rabies virus. Virology 209:569-79
195. Gilkeson GS, Conover J, Halpern M, Pisetsky DS, Feagin A, Klinman DM. 1998. Effects of bacterial DNA on cytokine production by (NZB/NZW)F1 mice. J. Immunol. 161:3890-95
196. Bachmaier K, Neu N, de la Maza LM, Pal S, Hessel A, Penninger JM. 1999. Chlamydia infections and heart disease linked through antigenic mimicry. Science 283:1335-39
197. Silverstein AM, Segal S. 1975. The ontogeny of antigen-specific T cells. J. Exp. Med. 142:802-4
198. Marodon G, Rocha B. 1994. Activation and 'deletion' of self-reactive mature and immature T cells during ontogeny of Mis-la mice: implications for neonatal tolerance induction. Int. Immunol. 6:1899-904
199. Silverstein AM. 1977. Ontogeny of the immune response: a perspective. In Development of Host Defenses, eds. MD Cooper, DH Dayton, pp. 1-10. New York: Raven
200. Sarzotti M, Robbins DS, Hoffman PM. 1996. Induction of protective CTL responses in newborn mice by a murine retro virus. Science 271:1726-28
201. Mor G, Yamshchikov G, Sedegah M, Takeno M, Wang R, Houghten RA, Hoffman S, Klinman DM. 1996. Induction of neonatal tolerance by plasmid DNA vaccination of mice. J. Clin. Invest. 98:2700-5
202. Ichino M, Mor G, Conover J, Weiss WR, Takeno M, Ishii KJ, Klinman DM. 1999. Factors associated with the development of neonatal tolerance after the administration of a plasmid DNA vaccine. J. Immunol. 162:3814-18
203. Klinman DM, Conover J, Bloom ET, Weiss W. 1998. Immunogenicity and efficacy of DNA vaccination in aged mice. J. Gerontol. 53:B281-86
204. Ishii KJ, Weiss W, Klinman DM. 1999. Prevention of neonatal tolerance by plasmid encoding GM-CSF. Vaccine. In press
205. Sarzotti M, Dean TA, Remington MP, Ly CD, Furth PA, Robbins DS. 1997. Induction of cytotoxic T cell responses in newborn mice by DNA immunization. Vaccine 15:795-97
206. Wang Y, Xiang Z, Pasquini S, Ertl HC. 1997. Immune response to neonatal genetic immunization. Virology 228: 278-84
207. Prince AM, Whalen R, Brotman B. 1997. Successful nucleic acid based immunization of newborn chimpanzees against hepatitis B virus. Vaccine 15:916-19
208. Davis HL, Brazolot Millan CL. 1997. DNA-based immunization against hepatitis B virus. Springer Semin, Immunopathol. 19:195-209
209. Bot A, Bot S, Bona C. 1998. Enhanced protection against influenza virus of mice immunized as newborns with a mixture of plasmids expressing hemagglutinin and nucleoprotein. Vaccine 16:1675-82
210. Manickan E, Yu Z, Rouse BT. 1997. DNA immunization of neonates induces immunity despite the presence of maternal antibody. J. Clin. Invest. 100:2371-75
211. Ishii KJ, Weiss WR, Ichino D, Verthelyi D, Klinman DM. 1999. Activity and safety of DNA plasmids encoding IL-4 and IFN-γ. Gene Ther. 6:237-44
212. U.S. Food and Drug Administration. Points to Consider, http://www.fda.gov/ cber/points.html
213. Hakim I, Levy S, Levy R. 1996. A nine-amino acid peptide from IL-1 β augments antitumor immune responses induced by protein and DNA vaccines. J. Immunol. 157:5503-11
214. Maecker HT, Umetsu DT, DeKruyff RH, Levy S. 1997. DNA vaccination with cytokine fusion constructs biases the immune response to ovalbumin. Vaccine 15:1687-96
215. Kim JJ, Trivedi NN, Nottingham LK, Morrison L, Tsai A, Hu Y, Mahalingam S, Dang K, Ahn L, Doyle NK, Wilson DM, Chattergoon MA, Chalian AA, Boyer JD, Agadjanyan MG, Weiner DB. 1998. Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens. Eur. J. Immunol. 28:1089-103
216. Raz E, Watanabe A, Baird SM, Eisenberg RA, Parr TB, Lotz M, Kipps TJ, Carson DA. 1993. Systemic immunological effects of cytokine genes injected into skeletal muscle. Proc. Natl. Acad. Sci. USA 90:4523-27
217. Chow YH, Huang WL, Chi WK, Chu YD, Tao MH. 1997. Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2. J. Virol. 71:169-78
218. Geissler M, Gesien A, Tokushige K, Wands JR. 1997. Enhancement of cellular and humoral immune responses to hepatitis C virus core protein using DNA-based vaccines augmented with cytokine-expressing plasmids. J. Immunol. 158:1231-37
219. Prayaga SK, Ford MJ, Haynes JR. 1997. Manipulation of HIV-1 gp120-specific immune responses elicited via gene gun-based DNA immunization. Vaccine 15:1349-52
220. Chow YH, Chiang BL, Lee YL, Chi WK, Lin WC, Chen YT, Tao MH. 1998. Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. J. Immunol. 160:1320-29
221. Kim JJ, Simbiri KA, Sin JI, Dang K, Oh J, Dentchev T, Lee D, Nottingham LK, Chalian AA, McCallus D, Ciccarelli E, Agadjanyan MG, Weiner DB. 1999. Cytokine molecular adjuvants modulate immune responses induced by DNA vaccine constructs for HIV-1 and SIV. J. Interferon Cytokine Res. 19:77-84
222. Larsen DL, Dybdahl-Sissoko N, McGregor MW, Drape R, Neumann V, Swain WF, Lunn DP, Olsen CW. 1998. Coadministration of DNA encoding interleukin-6 and hemagglutinin confers protection from influenza virus challenge in mice. J. Virol. 72:1704-8
223. Hengge UR, Chan EF, Foster RA, Walker PS, Vogel JC. 1995. Cytokine gene expression in epidermis with biological effects following injection of naked DNA. Nat. Genet. 10:161-66
224. Rogy MA, Auffenberg T, Espat NJ, Philip R, Remick D, Wollenberg GK, Copeland EM III, Moldawer LL. 1995. Human tumor necrosis factor receptor (p55) and interleukin 10 gene transfer in the mouse reduces mortality to lethal endotoxemia and also attenuates local inflammatory responses. J. Exp. Med. 181:2289-93
225. Daheshia M, Kuklin N, Kanangat S, Manickan E, Rouse BT. 1997. Suppression of ongoing ocular inflammatory disease by topical administration of plasmid DNA encoding IL-10. J. Immunol. 159:1945-52
226. Manickan E, Daheshia M, Kuklin N, Chun S, Rouse BT. 1998. Modulation of virus-induced delayed-type hypersensitivity by plasmid DNA encoding the cytokine interleukin-10. Immunology 94:129-34
227. Kim JJ, Ayyavoo V, Bagarazzi ML, Chattergoon MA, Dang K, Wang B, Boyer JD, Weiner DB. 1997. In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen. J. Immunol. 158:816-26
228. Gurunathan S, Irvine KR, Wu CY, Cohen JI, Thomas E, Prussin C, Restifo NP, Seder RA. 1998. CD40 ligand/trimer DNA enhances both humoral and cellular immune responses and induces protective immunity to infectious and tumor challenge. J. Immunol. 161:4563-71
229. Tsuji T, Hamajima K, Fukushima J, Xin KQ, Ishii N, Aoki I, Ishigatsubo Y, Tani K, Kawamoto S, Nitta Y, Miyazaki J, Koff WC, Okubo T, Okuda K. 1997. Enhancement of cell-mediated immunity against HIV-1 induced by coinoculation of plasmid-encoded HIV-1 antigen with plasmid expressing IL-12. J. Immunol. 158:4008-13
230. Rakhmilevich AL, Turner J, Ford MJ, McCabe D, Sun WH, Sondel PM, Grota K, Yang NS. 1996. Gene gun-mediated skin transfection with interleukin 12 gene results in regression of established primaty and metastatic murine tumors. Proc. Natl. Acad. Sci. USA 93: 6291-96
231. Kim JJ, Ayyavoo V, Bagarazzi ML, Chattergoon M, Boyer JD, Wang B, Weiner DB. 1997. Development of a multicomponent candidate vaccine for HIV-1. Vaccine 15:879-83
232. Svanholm C, Lowenadler B, Wigzell H. 1997. Amplification of T-cell and antibody responses in DNA-based immunization with HIV-1 Nef by co-injection with a GM-CSF expression vector. Scand. J. Immunol. 46:298-303
233. Weiss WR, Ishii KJ, Hedstrom RC, Sedegah M, Ichino M, Barnhart K, Klinman DM, Hoffman SL. 1998. A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine. J. Immunol. 161:2325-32
234. Lee AH, Suh YS, Sung YC. 1999. DNA inoculations with HIV-1 recombinant genomes that express cytokine genes enhance HIV-1 specific immune responses. Vaccine 17:473-79
235. Xiang Z, Ertl HC. 1995. Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines. Immunity 2:129-35
236. Song XY, Gu M, Jin WW, Klinman DM, Wahl SM. 1998. Plasmid DNA encoding transforming growth factor-β1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model. J. Clin. Invest. 101:2615-21
237. Lim YS, Kang BY Kim EJ, Kim SH, Hwang SY, Kim TS. 1998. Potentiation of antigen specific, Th1 immune responses by multiple DNA vaccination with ovalbumin/interferon-γ hybrid construct. Immunology 94:135-41
238. Yeow WS, Lawson CM, Beilharz MW. 1998. Antiviral activities of individual murine IFN-α subtypes in vivo: intramuscular injection of IFN expression constructs reduces cytomegalovirus replication. J. Immunol. 160:2932-39
239. Horton HM, Anderson D, Hernandez P, Bamhart KM, Norman JA, Parker SE. 1999. A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon α Proc. Natl. Acad. Sci. USA 96:1553-58
240. Tsuji T, Hamajima K, Ishii N, Aoki I, Fukushima J, Xin KQ, Kawamoto S, Sasaki S, Matsunaga K, Ishigatsubo Y, Tani K, Okubo T, Okuda K. 1997. Immunomodulatory effects of a plasmid expressing B7-2 on human immunodeficiency virus-1-specific cell-mediated immunity induced by a plasmid encoding the viral antigen. Eur. J. Immunol. 27:782-87
241. Kim JJ, Bagarazzi ML, Trivedi N, Hu Y, Kazahaya K, Wilson DM, Ciccarelli R, Chattergoon MA, Dang K, Mahalingam S, Chalian AA, Agadjanyan MG, Boyer JD, Wang B, Weiner DB. 1997. Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes. Nat. Biotechnol. 15:641-46
242. Corr M, Tighe H, Lee D, Dudler J, Trieu M, Brinson DC, Carson DA. 1997. Costimulation provided by DNA immunization enhances antitumor immunity. J. Immunol. 159:4999-5004
243. Horspool JH, Perrin PJ, Woodcock JB, Cox JH, King CL, June CH, Harlan DM, St. Louis DC, Lee KP. 1998. Nucleic acid vaccine-induced immune responses require CD28 costimulation and are regulated by CTLA4. J. Immunol. 160:2706-14
244. Mendoza RB, Cantwell MJ, Kipps TJ. 1997. Immunostimulatory effects of a plasmid expressing CD40 ligand (CD154) on gene immunization. J. Immunol. 159:5777-81
245. Kim JJ, Tsai A, Nottingham LK, Mornson L, Cunning DM, Oh J, Lee DJ, Dang K, Dentchev T, Chalian AA, Agadjanyan MG, Weiner DB. 1999. Intracellular adhesion molecule-1 modulates β-chemokines and directly costimulates T cells in vivo. J. Clin. Invest. 103:869-77
246. Boyle JS, Brady JL, Lew AM. 1998. Enhanced responses to a DNA vaccine encoding a fusion antigen that is directed to sites of immune induction. Nature 392:408-11