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Using Plasmids as DNA Vaccines for Infectious Diseases

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  • Authors: John S. Tregoning1, Ekaterina Kinnear2
  • Editors: Marcelo Tolmasky3, Juan Carlos Alonso4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Mucosal Infection and Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London W2 1PG, United Kingdom; 2: Mucosal Infection and Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London W2 1PG, United Kingdom; 3: California State University, Fullerton, CA; 4: Centro Nacional de Biotecnología, Cantoblanco, Madrid, Spain
  • Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0028-2014
  • Received 01 October 2014 Accepted 03 October 2014 Published 28 November 2014
  • John S. Tregoning, john.tregoning@imperial.ac.uk
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  • Abstract:

    DNA plasmids can be used to induce a protective (or therapeutic) immune response by delivering genes encoding vaccine antigens. That naked DNA (without the refinement of coat proteins or host evasion systems) can cross from outside the cell into the nucleus and be expressed is particularly remarkable given the sophistication of the immune system in preventing infection by pathogens. As a result of the ease, low cost, and speed of custom gene synthesis, DNA vaccines dangle a tantalizing prospect of the next wave of vaccine technology, promising individual designer vaccines for cancer or mass vaccines with a rapid response time to emerging pandemics. There is considerable enthusiasm for the use of DNA vaccination as an approach, but this enthusiasm should be tempered by the successive failures in clinical trials to induce a potent immune response. The technology is evolving with the development of improved delivery systems that increase expression levels, particularly electroporation and the incorporation of genetically encoded adjuvants. This review will introduce some key concepts in the use of DNA plasmids as vaccines, including how the DNA enters the cell and is expressed, how it induces an immune response, and a summary of clinical trials with DNA vaccines. The review also explores the advances being made in vector design, delivery, formulation, and adjuvants to try to realize the promise of this technology for new vaccines. If the immunogenicity and expression barriers can be cracked, then DNA vaccines may offer a step change in mass vaccination.

  • Citation: Tregoning J, Kinnear E. 2014. Using Plasmids as DNA Vaccines for Infectious Diseases. Microbiol Spectrum 2(6):PLAS-0028-2014. doi:10.1128/microbiolspec.PLAS-0028-2014.

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References

1. Orth G, Atanasiu P, Boiron M, Rebiere JP, Paoletti C. 1964. Infectious and oncogenic effect of DNA extracted from cells infected with polyoma virus. Proc Soc Exp Biol Med 115:1090–1095. [PubMed][CrossRef]
2. Israel MA, Chan HW, Hourihan SL, Rowe WP, Martin MA. 1979. Biological activity of polyoma viral DNA in mice and hamsters. J Virol 29:990–996. [PubMed]
3. Will H, Cattaneo R, Darai G, Deinhardt F, Schellekens H, Schaller H. 1985. Infectious hepatitis B virus from cloned DNA of known nucleotide sequence. Proc Natl Acad Sci USA 82:891–895. [PubMed][CrossRef]
4. Tang DC, DeVit M, Johnston SA. 1992. Genetic immunization is a simple method for eliciting an immune response. Nature 356:152–154. [PubMed][CrossRef]
5. Wang B, Ugen KE, Srikantan V, Agadjanyan MG, Dang K, Refaeli Y, Sato AI, Boyer J, Williams WV, Weiner DB. 1993. Gene inoculation generates immune responses against human immunodeficiency virus type 1. Proc Natl Acad Sci USA 90:4156–4160. [PubMed][CrossRef]
6. 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 90:11478–11482. [PubMed][CrossRef]
7. Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, DeWitt CM, Friedman A, et al. 1993. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259:1745–1749. [PubMed][CrossRef]
8. Rice J, Ottensmeier CH, Stevenson FK. 2008. DNA vaccines: precision tools for activating effective immunity against cancer. Nat Rev Cancer 8:108–120. [PubMed][CrossRef]
9. Chua KY, Kuo IC, Huang CH. 2009. DNA vaccines for the prevention and treatment of allergy. Curr Opin Allergy Clin Immunol 9:50–54. [PubMed][CrossRef]
10. Ramshaw IA, Fordham SA, Bernard CC, Maguire D, Cowden WB, Willenborg DO. 1997. DNA vaccines for the treatment of autoimmune disease. Immunol Cell Biol 75:409–413. [PubMed][CrossRef]
11. He Y, Racz R, Sayers S, Lin Y, Todd T, Hur J, Li X, Patel M, Zhao B, Chung M, Ostrow J, Sylora A, Dungarani P, Ulysse G, Kochhar K, Vidri B, Strait K, Jourdian GW, Xiang Z. 2014. Updates on the web-based VIOLIN vaccine database and analysis system. Nucleic Acids Res 42:D1124-D1132. [PubMed][CrossRef]
12. Czar MJ, Anderson JC, Bader JS, Peccoud J. 2009. Gene synthesis demystified. Trends Biotechnol 27:63–72. [PubMed][CrossRef]
13. Davis BS, Chang GJ, Cropp B, Roehrig JT, Martin DA, Mitchell CJ, Bowen R, Bunning ML. 2001. West Nile virus recombinant DNA vaccine protects mouse and horse from virus challenge and expresses in vitro a noninfectious recombinant antigen that can be used in enzyme-linked immunosorbent assays. J Virol 75:4040–4047. [PubMed][CrossRef]
14. Garver KA, LaPatra SE, Kurath G. 2005. Efficacy of an infectious hematopoietic necrosis (IHN) virus DNA vaccine in Chinook Oncorhynchus tshawytscha and sockeye O. nerka salmon. Dis Aquat Organ 64:13–22. [PubMed][CrossRef]
15. Grosenbaugh DA, Leard AT, Bergman PJ, Klein MK, Meleo K, Susaneck S, Hess PR, Jankowski MK, Jones PD, Leibman NF, Johnson MH, Kurzman ID, Wolchok JD. 2011. Safety and efficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment for oral malignant melanoma in dogs following surgical excision of the primary tumor. Am J Vet Res 72:1631–1638. [PubMed][CrossRef]
16. Denies S, Sanders NN. 2012. Recent progress in canine tumor vaccination: potential applications for human tumor vaccines. Exp Rev Vaccines 11:1375–1386. [PubMed][CrossRef]
17. Nichols WW, Ledwith BJ, Manam SV, Troilo PJ. 1995. Potential DNA vaccine integration into host cell genome. Ann NY Acad Sci 772:30–39. [PubMed][CrossRef]
18. Bertino P, Urschitz J, Hoffmann FW, You BR, Rose AH, Park WH, Moisyadi S, Hoffmann PR. 2014. Vaccination with a piggyBac plasmid with transgene integration potential leads to sustained antigen expression and CD8(+) T cell responses. Vaccine 32:1670–1677. [PubMed][CrossRef]
19. Hovav AH, Panas MW, Rahman S, Sircar P, Gillard G, Cayabyab MJ, Letvin NL. 2007. Duration of antigen expression in vivo following DNA immunization modifies the magnitude, contraction, and secondary responses of CD8+ T lymphocytes. J Immunol 179:6725–6733. [PubMed][CrossRef]
20. USA FDA. 2007. Guidance for industry: considerations for plasmid DNA vaccines for infectious disease indications. Biotechnol Law Rep 26:641–647. [CrossRef]
21. Roberston J, Ackland J, Holm A. 2007. Guidelines for assuring the quality and nonclinical safety evaluation of DNA vaccines. WHO Tech Rep Ser 941:57–81.
22. Vandermeulen G, Marie C, Scherman D, Preat V. 2011. New generation of plasmid backbones devoid of antibiotic resistance marker for gene therapy trials. Mol Ther 19:1942–1949. [PubMed][CrossRef]
23. Cunningham DS, Koepsel RR, Ataai MM, Domach MM. 2009. Factors affecting plasmid production in Escherichia coli from a resource allocation standpoint. Microb Cell Fact 8:27. [PubMed][CrossRef]
24. Josefsberg JO, Buckland B. 2012. Vaccine process technology. Biotechnol Bioeng 109:1443–1460. [PubMed][CrossRef]
25. Prather KJ, Sagar S, Murphy J, Chartrain M. 2003. Industrial scale production of plasmid DNA for vaccine and gene therapy: plasmid design, production, and purification. Enzyme Microb Tech 33:865–883. [CrossRef]
26. Glenting J, Wessels S. 2005. Ensuring safety of DNA vaccines. Microb Cell Fact 4:26. [PubMed][CrossRef]
27. Racz R, Li X, Patel M, Xiang Z, He Y. 2014. DNAVaxDB: the first web-based DNA vaccine database and its data analysis. BMC Bioinformatics 15:S2. [PubMed][CrossRef]
28. Dupuis M, Denis-Mize K, Woo C, Goldbeck C, Selby MJ, Chen M, Otten GR, Ulmer JB, Donnelly JJ, Ott G, McDonald DM. 2000. Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice. J Immunol 165:2850–2858. [PubMed][CrossRef]
29. Leamy VL, Martin T, Mahajan R, Vilalta A, Rusalov D, Hartikka J, Bozoukova V, Hall KD, Morrow J, Rolland AP, Kaslow DC, Lalor PA. 2006. Comparison of rabbit and mouse models for persistence analysis of plasmid-based vaccines. Hum Vaccin 2:113–118. [PubMed][CrossRef]
30. Coban C, Kobiyama K, Jounai N, Tozuka M, Ishii KJ. 2013. DNA vaccines: a simple DNA sensing matter? Hum Vaccin Immunother 9:2216–2221. [PubMed][CrossRef]
31. Wang Y, Guo Y, Wang X, Huang J, Shang J, Sun S. 2011. Human serum amyloid P functions as a negative regulator of the innate and adaptive immune responses to DNA vaccines. J Immunol 186:2860–2870. [PubMed][CrossRef]
32. Wiethoff CM, Middaugh CR. 2003. Barriers to nonviral gene delivery. J Pharm Sci 92:203–217. [PubMed][CrossRef]
33. Kim BM, Lee DS, Choi JH, Kim CY, Son M, Suh YS, Baek KH, Park KS, Sung YC, Kim WB. 2003. In vivo kinetics and biodistribution of a HIV-1 DNA vaccine after administration in mice. Arch Pharm Res 26:493–498. [PubMed][CrossRef]
34. Zhang HY, Sun SH, Guo YJ, Chen ZH, Huang L, Gao YJ, Wan B, Zhu WJ, Xu GX, Wang JJ. 2005. Tissue distribution of a plasmid DNA containing epitopes of foot-and-mouth disease virus in mice. Vaccine 23:5632–5640. [PubMed][CrossRef]
35. Condon C, Watkins SC, Celluzzi CM, Thompson K, Falo LD, Jr. 1996. DNA-based immunization by in vivo transfection of dendritic cells. Nat Med 2:1122–1128. [PubMed][CrossRef]
36. Wolff JA, Dowty ME, Jiao S, Repetto G, Berg RK, Ludtke JJ, Williams P, Slautterback DB. 1992. Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle. J Sci 103(Pt 4):1249–1259. [PubMed]
37. Budker V, Budker T, Zhang G, Subbotin V, Loomis A, Wolff JA. 2000. Hypothesis: naked plasmid DNA is taken up by cells in vivo by a receptor-mediated process. J Gene Med 2:76–88. [PubMed][CrossRef]
38. Latz E, Schoenemeyer A, Visintin A, Fitzgerald KA, Monks BG, Knetter CF, Lien E, Nilsen NJ, Espevik T, Golenbock DT. 2004. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol 5:190–198. [PubMed][CrossRef]
39. Lechardeur D, Verkman AS, Lukacs GL. 2005. Intracellular routing of plasmid DNA during non-viral gene transfer. Adv Drug Del Rev 57:755–767. [PubMed]
40. Mui B, Ahkong QF, Chow L, Hope MJ. 2000. Membrane perturbation and the mechanism of lipid-mediated transfer of DNA into cells. Biochim Biophys Acta 1467:281–292. [PubMed][CrossRef]
41. Trombone AP, Silva CL, Lima KM, Oliver C, Jamur MC, Prescott AR, Coelho-Castelo AA. 2007. Endocytosis of DNA-Hsp65 alters the pH of the late endosome/lysosome and interferes with antigen presentation. PloS One 2:e923. doi:10.1371/journal.pone.0000923. [PubMed][CrossRef]
42. Lechardeur D, Sohn KJ, Haardt M, Joshi PB, Monck M, Graham RW, Beatty B, Squire J, O'Brodovich H, Lukacs GL. 1999. Metabolic instability of plasmid DNA in the cytosol: a potential barrier to gene transfer. Gene Ther 6:482–497. [PubMed][CrossRef]
43. Capecchi MR. 1980. High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell 22:479–488. [PubMed][CrossRef]
44. Wilke M, Fortunati E, van den Broek M, Hoogeveen AT, Scholte BJ. 1996. Efficacy of a peptide-based gene delivery system depends on mitotic activity. Gene Ther 3:1133–1142. [PubMed]
45. van der Aa MA, Mastrobattista E, Oosting RS, Hennink WE, Koning GA, Crommelin DJ. 2006. The nuclear pore complex: the gateway to successful nonviral gene delivery. Pharm Res 23:447–459. [PubMed][CrossRef]
46. Talcott B, Moore MS. 1999. Getting across the nuclear pore complex. Trends Cell Biol 9:312–318. [PubMed][CrossRef]
47. Dean DA. 1997. Import of plasmid DNA into the nucleus is sequence specific. Exp Cell Res 230:293–302. [PubMed][CrossRef]
48. Gurtler C, Bowie AG. 2013. Innate immune detection of microbial nucleic acids. Trends Microbiol 21:413–420. [PubMed][CrossRef]
49. Babiuk S, Mookherjee N, Pontarollo R, Griebel P, van Drunen Littel-van den Hurk S, Hecker R, Babiuk L. 2004. TLR9-/- and TLR9+/+ mice display similar immune responses to a DNA vaccine. Immunology 113:114–120. [PubMed][CrossRef]
50. Ishii KJ, Kawagoe T, Koyama S, Matsui K, Kumar H, Kawai T, Uematsu S, Takeuchi O, Takeshita F, Coban C, Akira S. 2008. TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Nature 451:725–729. [PubMed][CrossRef]
51. Ishikawa H, Ma Z, Barber GN. 2009. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461:788–792. [PubMed][CrossRef]
52. Davis HL, Millan CL, Watkins SC. 1997. Immune-mediated destruction of transfected muscle fibers after direct gene transfer with antigen-expressing plasmid DNA. Gene Ther 4:181–188. [PubMed][CrossRef]
53. Palumbo RN, Zhong X, Wang C. 2012. Polymer-mediated DNA vaccine delivery via bystander cells requires a proper balance between transfection efficiency and cytotoxicity. J Control Release 157:86–93. [PubMed][CrossRef]
54. Cho JH, Youn JW, Sung YC. 2001. Cross-priming as a predominant mechanism for inducing CD8(+) T cell responses in gene gun DNA immunization. J Immunol 167:5549–5557. [PubMed][CrossRef]
55. Fredriksen AB, Sandlie I, Bogen B. 2012. Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells. Front Oncol 2:154. [PubMed][CrossRef]
56. Grodeland G, Mjaaland S, Roux KH, Fredriksen AB, Bogen B. 2013. DNA vaccine that targets hemagglutinin to MHC class II molecules rapidly induces antibody-mediated protection against influenza. J Immunol 191:3221–3231. [PubMed][CrossRef]
57. McCluskie MJ, Brazolot Millan CL, Gramzinski RA, Robinson HL, Santoro JC, Fuller JT, Widera G, Haynes JR, Purcell RH, Davis HL. 1999. Route and method of delivery of DNA vaccine influence immune responses in mice and non-human primates. Mol Med 5:287–300. [PubMed]
58. Combadiere B, Liard C. 2011. Transcutaneous and intradermal vaccination. Hum Vaccin 7:811–827. [PubMed][CrossRef]
59. Romani N, Flacher V, Tripp CH, Sparber F, Ebner S, Stoitzner P. 2012. Targeting skin dendritic cells to improve intradermal vaccination. Curr Top Microbiol Immunol 351:113–138. [PubMed][CrossRef]
60. Enama ME, Ledgerwood JE, Novik L, Nason MC, Gordon IJ, Holman L, Bailer RT, Roederer M, Koup RA, Mascola JR, Nabel GJ, Graham BS, VRC 011 Study Team. 2014. Phase I randomized clinical trial of VRC DNA and rAd5 HIV-1 vaccine delivery by intramuscular (i.m.), subcutaneous (s.c.) and intradermal (i.d.) administration (VRC 011). PloS One 9:e91366. doi:10.1371/journal.pone.0091366. [PubMed][CrossRef]
61. Mahe B, Vogt A, Liard C, Duffy D, Abadie V, Bonduelle O, Boissonnas A, Sterry W, Verrier B, Blume-Peytavi U, Combadiere B. 2008. Nanoparticle-based targeting of vaccine compounds to skin antigen-presenting cells by hair follicles and their transport in mice. J Invest Dermatol 129:1156–1164. [PubMed][CrossRef]
62. Budker V, Zhang G, Danko I, Williams P, Wolff J. 1998. The efficient expression of intravascularly delivered DNA in rat muscle. Gene Ther 5:272–276. [PubMed][CrossRef]
63. Hodges BL, Scheule RK. 2003. Hydrodynamic delivery of DNA. Exp Opin Biol Ther 3:911–918. [PubMed][CrossRef]
64. Hegge JO, Wooddell CI, Zhang G, Hagstrom JE, Braun S, Huss T, Sebestyen MG, Emborg ME, Wolff JA. 2010. Evaluation of hydrodynamic limb vein injections in nonhuman primates. Hum Gene Ther 21:829–842. [PubMed][CrossRef]
65. Bivas-Benita M, Ottenhoff TH, Junginger HE, Borchard G. 2005. Pulmonary DNA vaccination: concepts, possibilities and perspectives. J Control Release 107:1–29. [PubMed][CrossRef]
66. Schautteet K, Stuyven E, Beeckman DS, Van Acker S, Carlon M, Chiers K, Cox E, Vanrompay D. 2011. Protection of pigs against Chlamydia trachomatis challenge by administration of a MOMP-based DNA vaccine in the vaginal mucosa. Vaccine 29:1399–1407. [PubMed][CrossRef]
67. Hamajima K, Hoshino Y, Xin KQ, Hayashi F, Tadokoro K, Okuda K. 2002. Systemic and mucosal immune responses in mice after rectal and vaginal immunization with HIV-DNA vaccine. Clin Immunol 102:12–18. [PubMed][CrossRef]
68. Mann JF, McKay PF, Arokiasamy S, Patel RK, Tregoning JS, Shattock RJ. 2013. Mucosal application of gp140 encoding DNA polyplexes to different tissues results in altered immunological outcomes in mice. PloS One 8:e67412. doi:10.1371/journal.pone.0067412. [PubMed][CrossRef]
69. Niethammer AG, Lubenau H, Mikus G, Knebel P, Hohmann N, Leowardi C, Beckhove P, Akhisaroglu M, Ge Y, Springer M, Grenacher L, Buchler MW, Koch M, Weitz J, Haefeli WE, Schmitz-Winnenthal FH. 2012. Double-blind, placebo-controlled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-receptor 2 in patients with stage IV and locally advanced pancreatic cancer. BMC Cancer 12:361. [PubMed][CrossRef]
70. Greenland JR, Letvin NL. 2007. Chemical adjuvants for plasmid DNA vaccines. Vaccine 25:3731–3741. [PubMed][CrossRef]
71. Wegmann F, Gartlan KH, Harandi AM, Brinckmann SA, Coccia M, Hillson WR, Kok WL, Cole S, Ho LP, Lambe T, Puthia M, Svanborg C, Scherer EM, Krashias G, Williams A, Blattman JN, Greenberg PD, Flavell RA, Moghaddam AE, Sheppard NC, Sattentau QJ. 2012. Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. Nat Biotechnol 30:883–888. [PubMed][CrossRef]
72. Klein K, Mann JF, Rogers P, Shattock RJ. 2014. Polymeric penetration enhancers promote humoral immune responses to mucosal vaccines. J Control Release 183:43–50. [PubMed][CrossRef]
73. Klencke B, Matijevic M, Urban RG, Lathey JL, Hedley ML, Berry M, Thatcher J, Weinberg V, Wilson J, Darragh T, Jay N, Da Costa M, Palefsky JM. 2002. Encapsulated plasmid DNA treatment for human papillomavirus 16-associated anal dysplasia: a phase I study of ZYC101. Clin Cancer Res 8:1028–1037. [PubMed]
74. Oyewumi MO, Kumar A, Cui Z. 2010. Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses. Exp Rev Vaccin 9:1095–1107. [PubMed][CrossRef]
75. Fenske DB, Cullis PR. 2008. Liposomal nanomedicines. Exp Opin Drug Deliv 5:25–44. [PubMed][CrossRef]
76. Smith LR, Wloch MK, Ye M, Reyes LR, Boutsaboualoy S, Dunne CE, Chaplin JA, Rusalov D, Rolland AP, Fisher CL, Al-Ibrahim MS, Kabongo ML, Steigbigel R, Belshe RB, Kitt ER, Chu AH, Moss RB. 2010. Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin. Vaccine 28:2565–2572. [PubMed][CrossRef]
77. Kheiri MT, Jamali A, Shenagari M, Hashemi H, Sabahi F, Atyabi F, Saghiri R. 2012. Influenza virosome/DNA vaccine complex as a new formulation to induce intra-subtypic protection against influenza virus challenge. Antiviral Res 95:229–236. [PubMed][CrossRef]
78. Schoen C, Stritzker J, Goebel W, Pilgrim S. 2004. Bacteria as DNA vaccine carriers for genetic immunization. Int J Med Microbiol 294:319–335. [PubMed][CrossRef]
79. 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 87:9568–9572. [PubMed][CrossRef]
80. Roy MJ, Wu MS, Barr LJ, Fuller JT, Tussey LG, Speller S, Culp J, Burkholder JK, Swain WF, Dixon RM, Widera G, Vessey R, King A, Ogg G, Gallimore A, Haynes JR, Heydenburg Fuller D. 2000. Induction of antigen-specific CD8+ T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine. Vaccine 19:764–778. [PubMed][CrossRef]
81. Boudreau EF, Josleyn M, Ullman D, Fisher D, Dalrymple L, Sellers-Myers K, Loudon P, Rusnak J, Rivard R, Schmaljohn C, Hooper JW. 2012. A phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for hemorrhagic fever with renal syndrome. Vaccine 30:1951–1958. [PubMed][CrossRef]
82. Rottinghaus ST, Poland GA, Jacobson RM, Barr LJ, Roy MJ. 2003. Hepatitis B DNA vaccine induces protective antibody responses in human non-responders to conventional vaccination. Vaccine 21:4604–4608. [PubMed][CrossRef]
83. Tacket CO, Roy MJ, Widera G, Swain WF, Broome S, Edelman R. 1999. Phase 1 safety and immune response studies of a DNA vaccine encoding hepatitis B surface antigen delivered by a gene delivery device. Vaccine 17:2826–2829. [PubMed][CrossRef]
84. Shergold OA, Fleck NA, King TS. 2006. The penetration of a soft solid by a liquid jet, with application to the administration of a needle-free injection. J Biomech 39:2593–2602. [PubMed][CrossRef]
85. Ginsberg BA, Gallardo HF, Rasalan TS, Adamow M, Mu Z, Tandon S, Bewkes BB, Roman RA, Chapman PB, Schwartz GK, Carvajal RD, Panageas KS, Terzulli SL, Houghton AN, Yuan JD, Wolchok JD. 2010. Immunologic response to xenogeneic gp100 DNA in melanoma patients: comparison of particle-mediated epidermal delivery with intramuscular injection. Clin Cancer Res 16:4057–4065. [PubMed][CrossRef]
86. Kutzler MA, Weiner DB. 2008. DNA vaccines: ready for prime time? Nat Rev Genet 9:776–788. [PubMed][CrossRef]
87. Grunwald T, Tenbusch M, Schulte R, Raue K, Wolf H, Hannaman D, de Swart RL, Uberla K, Stahl-Hennig C. 2014. Novel vaccine regimen elicits strong airway immune responses and control of respiratory syncytial virus in nonhuman primates. J Virol 88:3997–4007. [PubMed][CrossRef]
88. Verstrepen BE, Bins AD, Rollier CS, Mooij P, Koopman G, Sheppard NC, Sattentau Q, Wagner R, Wolf H, Schumacher TNM, Heeney JL, Haanen JBAG. 2008. Improved HIV-1 specific T-cell responses by short-interval DNA tattooing as compared to intramuscular immunization in non-human primates. Vaccine 26:3346–3351. [PubMed][CrossRef]
89. DeMuth PC, Min Y, Huang B, Kramer JA, Miller AD, Barouch DH, Hammond PT, Irvine DJ. 2013. Polymer multilayer tattooing for enhanced DNA vaccination. Nat Mat 12:367–376. [PubMed][CrossRef]
90. van Drunen Littel-van den Hurk S, Hannaman D. 2010. Electroporation for DNA immunization: clinical application. Exp Rev Vaccines 9:503–517. [PubMed][CrossRef]
91. Gothelf A, Gehl J. 2012. What you always needed to know about electroporation based DNA vaccines. Hum Vaccines Immunother 8:1694–1702. [PubMed][CrossRef]
92. Heller R, Jaroszeski M, Atkin A, Moradpour D, Gilbert R, Wands J, Nicolau C. 1996. In vivo gene electroinjection and expression in rat liver. FEBS Lett 389:225–228. [PubMed][CrossRef]
93. Widera G, Austin M, Rabussay D, Goldbeck C, Barnett SW, Chen M, Leung L, Otten GR, Thudium K, Selby MJ, Ulmer JB. 2000. Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J Immunol 164:4635–4640. [PubMed][CrossRef]
94. Ahlen G, Soderholm J, Tjelle T, Kjeken R, Frelin L, Hoglund U, Blomberg P, Fons M, Mathiesen I, Sallberg M. 2007. In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural 3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ T cells. J Immunol 179:4741–4753. [PubMed][CrossRef]
95. Vasan S, Hurley A, Schlesinger SJ, Hannaman D, Gardiner DF, Dugin DP, Boente-Carrera M, Vittorino R, Caskey M, Andersen J, Huang Y, Cox JH, Tarragona-Fiol T, Gill DK, Cheeseman H, Clark L, Dally L, Smith C, Schmidt C, Park HH, Kopycinski JT, Gilmour J, Fast P, Bernard R, Ho DD. 2011. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PloS One 6:e19252. doi:10.1371/journal.pone.0019252. [PubMed][CrossRef]
96. Pavlenko M, Roos AK, Lundqvist A, Palmborg A, Miller AM, Ozenci V, Bergman B, Egevad L, Hellstrom M, Kiessling R, Masucci G, Wersall P, Nilsson S, Pisa P. 2004. A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer. Br J Cancer 91:688–694. [PubMed]
97. Trimble CL, Peng S, Kos F, Gravitt P, Viscidi R, Sugar E, Pardoll D, Wu TC. 2009. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res 15:361–367. [PubMed][CrossRef]
98. Garmory HS, Brown KA, Titball RW. 2003. DNA vaccines: improving expression of antigens. Genet Vaccines Ther 1:2. [PubMed][CrossRef]
99. Manoj S, Babiuk LA, van Drunen Littel-van den Hurk S. 2004. Approaches to enhance the efficacy of DNA vaccines. Crit Rev Clin Lab Sci 41:1–39. [PubMed][CrossRef]
100. Yew NS, Wysokenski DM, Wang KX, Ziegler RJ, Marshall J, McNeilly D, Cherry M, Osburn W, Cheng SH. 1997. Optimization of plasmid vectors for high-level expression in lung epithelial cells. Hum Gene Ther 8:575–584. [PubMed][CrossRef]
101. Nagata T, Uchijima M, Yoshida A, Kawashima M, Koide Y. 1999. Codon optimization effect on translational efficiency of DNA vaccine in mammalian cells: analysis of plasmid DNA encoding a CTL epitope derived from microorganisms. Biochem Biophys Res Commun 261:445–451. [PubMed][CrossRef]
102. Goodwin EC, Rottman FM. 1992. The 3′-flanking sequence of the bovine growth hormone gene contains novel elements required for efficient and accurate polyadenylation. J Biol Chem 267:16330–16334. [PubMed]
103. Williams JA, Carnes AE, Hodgson CP. 2009. Plasmid DNA vaccine vector design: impact on efficacy, safety and upstream production. Biotechnol Adv 27:353–370. [PubMed][CrossRef]
104. Carvalho JA, Azzoni AR, Prazeres DMF, Monteiro GA. 2010. Comparative analysis of antigen-targeting sequences used in DNA vaccines. Mol Biotechnol 44:204–212. [PubMed][CrossRef]
105. Luo D, Saltzman WM. 2000. Synthetic DNA delivery systems. Nat Biotechnol 18:33–37. [PubMed][CrossRef]
106. Scheiermann J, Klinman DM. 2014. Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer. Vaccine 32:6377–6389. doi:10.1016/j.vaccine.2014.06.065. [PubMed][CrossRef]
107. Klinman DM, Yamshchikov G, Ishigatsubo Y. 1997. Contribution of CpG motifs to the immunogenicity of DNA vaccines. J Immunol 158:3635–3639. [PubMed]
108. Martinez-Alonso S, Martinez-Lopez A, Estepa A, Cuesta A, Tafalla C. 2011. The introduction of multi-copy CpG motifs into an antiviral DNA vaccine strongly up-regulates its immunogenicity in fish. Vaccine 29:1289–1296. [PubMed][CrossRef]
109. Miyabe H, Hyodo M, Nakamura T, Sato Y, Hayakawa Y, Harashima H. 2014. A new adjuvant delivery system ‘cyclic di-GMP/YSK05 liposome’ for cancer immunotherapy. J Controll Release 184:20–27. [PubMed][CrossRef]
110. Khosroshahi KH, Ghaffarifar F, Sharifi Z, D'Souza S, Dalimi A, Hassan ZM, Khoshzaban F. 2012. Comparing the effect of IL-12 genetic adjuvant and alum non-genetic adjuvant on the efficiency of the cocktail DNA vaccine containing plasmids encoding SAG-1 and ROP-2 of Toxoplasma gondii. Parasitol Res 111:403–411. [PubMed][CrossRef]
111. Ott G, Singh M, Kazzaz J, Briones M, Soenawan E, Ugozzoli M, O'Hagan DT. 2002. A cationic sub-micron emulsion (MF59/DOTAP) is an effective delivery system for DNA vaccines. J Controll Release 79:1–5. [PubMed][CrossRef]
112. Kwissa M, Amara RR, Robinson HL, Moss B, Alkan S, Jabbar A, Villinger F, Pulendran B. 2007. Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus. J Exp Med 204:2733–2746. [PubMed][CrossRef]
113. Otero M, Calarota SA, Felber B, Laddy D, Pavlakis G, Boyer JD, Weiner DB. 2004. Resiquimod is a modest adjuvant for HIV-1 gag-based genetic immunization in a mouse model. Vaccine 22:1782–1790. [PubMed][CrossRef]
114. Sun J, Hou J, Li D, Liu Y, Hu N, Hao Y, Fu J, Hu Y, Shao Y. 2013. Enhancement of HIV-1 DNA vaccine immunogenicity by BCG-PSN, a novel adjuvant. Vaccine 31:472–479. [PubMed][CrossRef]
115. Abdulhaqq SA, Weiner DB. 2008. DNA vaccines: developing new strategies to enhance immune responses. Immunol Res 42:219–232. [PubMed][CrossRef]
116. Baden LR, Blattner WA, Morgan C, Huang Y, Defawe OD, Sobieszczyk ME, Kochar N, Tomaras GD, McElrath MJ, Russell N, Brandariz K, Cardinali M, Graham BS, Barouch DH, Dolin R, NIAID HIV Vaccine Trials Network 044 Study Team. 2011. Timing of plasmid cytokine (IL-2/Ig) administration affects HIV-1 vaccine immunogenicity in HIV-seronegative subjects. J Infect Dis 204:1541–1549. [PubMed][CrossRef]
117. Kalams SA, Parker SD, Elizaga M, Metch B, Edupuganti S, Hural J, De Rosa S, Carter DK, Rybczyk K, Frank I, Fuchs J, Koblin B, Kim DH, Joseph P, Keefer MC, Baden LR, Eldridge J, Boyer J, Sherwat A, Cardinali M, Allen M, Pensiero M, Butler C, Khan AS, Yan J, Sardesai NY, Kublin JG, Weiner DB, NIAID HIV Vaccine Trials Network. 2013. Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery. J Infect Dis 208:818–829. [PubMed][CrossRef]
118. Richie TL, Charoenvit Y, Wang R, Epstein JE, Hedstrom RC, Kumar S, Luke TC, Freilich DA, Aguiar JC, Sacci JB, Jr, Sedegah M, Nosek RA, Jr, De La Vega P, Berzins MP, Majam VF, Abot EN, Ganeshan H, Richie NO, Banania JG, Baraceros MF, Geter TG, Mere R, Bebris L, Limbach K, Hickey BW, Lanar DE, Ng J, Shi M, Hobart PM, Norman JA, Soisson LA, Hollingdale MR, Rogers WO, Doolan DL, Hoffman SL. 2012. Clinical trial in healthy malaria-naive adults to evaluate the safety, tolerability, immunogenicity and efficacy of MuStDO5, a five-gene, sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with escalating dose human GM-CSF DNA. Hum Vaccin Immunother 8:1564–1584. [PubMed][CrossRef]
119. 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 15:641–646. [PubMed][CrossRef]
120. Zhai YZ, Zhou Y, Ma L, Feng GH. 2013. The dominant roles of ICAM-1-encoding gene in DNA vaccination against Japanese encephalitis virus are the activation of dendritic cells and enhancement of cellular immunity. Cell Immunol 281:1–10. [PubMed][CrossRef]
121. Saha S, Takeshita F, Matsuda T, Jounai N, Kobiyama K, Matsumoto T, Sasaki S, Yoshida A, Xin KQ, Klinman DM, Uematsu S, Ishii KJ, Akira S, Okuda K. 2007. Blocking of the TLR5 activation domain hampers protective potential of flagellin DNA vaccine. J Immunol 179:1147–1154. [PubMed][CrossRef]
122. Luke JM, Simon GG, Soderholm J, Errett JS, August JT, Gale M, Jr, Hodgson CP, Williams JA. 2011. Coexpressed RIG-I agonist enhances humoral immune response to influenza virus DNA vaccine. J Virol 85:1370–1383. [PubMed][CrossRef]
123. Kalams SA, Parker S, Jin X, Elizaga M, Metch B, Wang M, Hural J, Lubeck M, Eldridge J, Cardinali M, Blattner WA, Sobieszczyk M, Suriyanon V, Kalichman A, Weiner DB, Baden LR, NIAID HIV Vaccine Trials Network. 2012. Safety and immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and/or IL-15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults. PloS One 7:e29231. doi:10.1371/journal.pone.0029231. [CrossRef]
124. Ledgerwood JE, Wei CJ, Hu Z, Gordon IJ, Enama ME, Hendel CS, McTamney PM, Pearce MB, Yassine HM, Boyington JC, Bailer R, Tumpey TM, Koup RA, Mascola JR, Nabel GJ, Graham BS, VRC 306 Study Team. 2011. DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials. Lancet Infect Dis 11:916–924. [PubMed][CrossRef]
125. Liu MA. 2011. DNA vaccines: an historical perspective and view to the future. Immunol Rev 239:62–84. [PubMed][CrossRef]
126. Muthumani K, Flingai S, Wise M, Tingey C, Ugen KE, Weiner DB. 2013. Optimized and enhanced DNA plasmid vector based in vivo construction of a neutralizing anti-HIV-1 envelope glycoprotein Fab. Hum Vaccin Immunother 9:2253–2262. [PubMed][CrossRef]
127. Tan GS, Krammer F, Eggink D, Kongchanagul A, Moran TM, Palese P. 2012. A pan-H1 anti-hemagglutinin monoclonal antibody with potent broad-spectrum efficacy in vivo. J Virol 86:6179–6188. [PubMed][CrossRef]
128. Graham BS, Koup RA, Roederer M, Bailer RT, Enama ME, Moodie Z, Martin JE, McCluskey MM, Chakrabarti BK, Lamoreaux L, Andrews CA, Gomez PL, Mascola JR, Nabel GJ, Vaccine Research Center 004 Study Team. 2006. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J Infect Dis 194:1650–1660. [PubMed][CrossRef]
129. Gorse GJ, Baden LR, Wecker M, Newman MJ, Ferrari G, Weinhold KJ, Livingston BD, Villafana TL, Li H, Noonan E, Russell ND, HIV Vaccine Trials Network. 2008. Safety and immunogenicity of cytotoxic T-lymphocyte poly-epitope, DNA plasmid (EP HIV-1090) vaccine in healthy, human immunodeficiency virus type 1 (HIV-1)-uninfected adults. Vaccine 26:215–223. [PubMed][CrossRef]
130. Graham BS, Enama ME, Nason MC, Gordon IJ, Peel SA, Ledgerwood JE, Plummer SA, Mascola JR, Bailer RT, Roederer M, Koup RA, Nabel GJ, VRC 008 Study Team. 2013. DNA vaccine delivered by a needle-free injection device improves potency of priming for antibody and CD8+ T-cell responses after rAd5 boost in a randomized clinical trial. PloS One 8:e59340. doi:10.1371/journal.pone.0059340. [CrossRef]
131. Rosenberg ES, Graham BS, Chan ES, Bosch RJ, Stocker V, Maenza J, Markowitz M, Little S, Sax PE, Collier AC, Nabel G, Saindon S, Flynn T, Kuritzkes D, Barouch DH, AIDS Clinical Trials Group A5187 Team. 2010. Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection. PloS One 5:e10555. doi:10.1371/journal.pone.0010555. [CrossRef]
132. Jin X, Newman MJ, De-Rosa S, Cooper C, Thomas E, Keefer M, Fuchs J, Blattner W, Livingston BD, McKinney DM, Noonan E, Decamp A, Defawe OD, Wecker M, NIAID HIV Vaccine Trials Network. 2009. A novel HIV T helper epitope-based vaccine elicits cytokine-secreting HIV-specific CD4+ T cells in a phase I clinical trial in HIV-uninfected adults. Vaccine 27:7080–7086. [PubMed][CrossRef]
133. Vasan S, Schlesinger SJ, Huang Y, Hurley A, Lombardo A, Chen Z, Than S, Adesanya P, Bunce C, Boaz M, Boyle R, Sayeed E, Clark L, Dugin D, Schmidt C, Song Y, Seamons L, Dally L, Ho M, Smith C, Markowitz M, Cox J, Gill DK, Gilmour J, Keefer MC, Fast P, Ho DD. 2010. Phase 1 safety and immunogenicity evaluation of ADVAX, a multigenic, DNA-based clade C/B′ HIV-1 candidate vaccine. PloS One 5:e8617. doi:10.1371/journal.pone.0008617. [CrossRef]
134. Casazza JP, Bowman KA, Adzaku S, Smith EC, Enama ME, Bailer RT, Price DA, Gostick E, Gordon IJ, Ambrozak DR, Nason MC, Roederer M, Andrews CA, Maldarelli FM, Wiegand A, Kearney MF, Persaud D, Ziemniak C, Gottardo R, Ledgerwood JE, Graham BS, Koup RA, VRC 101 Study Team. 2013. Therapeutic vaccination expands and improves the function of the HIV-specific memory T-cell repertoire. J Infect Dis 207:1829–1840. [PubMed][CrossRef]
135. Beckett CG, Tjaden J, Burgess T, Danko JR, Tamminga C, Simmons M, Wu SJ, Sun P, Kochel T, Raviprakash K, Hayes CG, Porter KR. 2011. Evaluation of a prototype dengue-1 DNA vaccine in a phase 1 clinical trial. Vaccine 29:960–968. [PubMed][CrossRef]
136. Goepfert PA, Elizaga ML, Sato A, Qin L, Cardinali M, Hay CM, Hural J, DeRosa SC, DeFawe OD, Tomaras GD, Montefiori DC, Xu Y, Lai L, Kalams SA, Baden LR, Frey SE, Blattner WA, Wyatt LS, Moss B, Robinson HL, National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network. 2011. Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis 203:610–619. [PubMed][CrossRef]
137. Koblin BA, Casapia M, Morgan C, Qin L, Wang ZM, Defawe OD, Baden L, Goepfert P, Tomaras GD, Montefiori DC, McElrath MJ, Saavedra L, Lau CY, Graham BS, NIAID HIV Vaccine Trials Network. 2011. Safety and immunogenicity of an HIV adenoviral vector boost after DNA plasmid vaccine prime by route of administration: a randomized clinical trial. PloS One 6:e24517. doi:10.1371/journal.pone.0024517. [PubMed][CrossRef]
138. Gorse GJ, Newman MJ, deCamp A, Hay CM, De Rosa SC, Noonan E, Livingston BD, Fuchs JD, Kalams SA, Cassis-Ghavami FL, NIAID HIV Vaccine Trials Network. 2012. DNA and modified vaccinia virus Ankara vaccines encoding multiple cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) are safe but weakly immunogenic in HIV-1-uninfected, vaccinia virus-naive adults. Clin Vaccine Immunol 19:649–658. [PubMed][CrossRef]
139. Godon O, Fontaine H, Kahi S, Meritet J, Scott-Algara D, Pol S, Michel M, Bourgine M. 2014. Immunological and antiviral responses after therapeutic DNA immunization in chronic hepatitis B patients efficiently treated by analogues. Mol Ther 22:675–684. [PubMed][CrossRef]
140. Mancini-Bourgine M, Fontaine H, Scott-Algara D, Pol S, Brechot C, Michel ML. 2004. Induction or expansion of T-cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers. Hepatology 40:874–882. [PubMed][CrossRef]
141. Chuang I, Sedegah M, Cicatelli S, Spring M, Polhemus M, Tamminga C, Patterson N, Guerrero M, Bennett JW, McGrath S, Ganeshan H, Belmonte M, Farooq F, Abot E, Banania JG, Huang J, Newcomer R, Rein L, Litilit D, Richie NO, Wood C, Murphy J, Sauerwein R, Hermsen CC, McCoy AJ, Kamau E, Cummings J, Komisar J, Sutamihardja A, Shi M, Epstein JE, Maiolatesi S, Tosh D, Limbach K, Angov E, Bergmann-Leitner E, Bruder JT, Doolan DL, King CR, Carucci D, Dutta S, Soisson L, Diggs C, Hollingdale MR, Ockenhouse CF, Richie TL. 2013. DNA prime/adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity. PloS One 8:e55571. doi:10.1371/journal.pone.0055571. [PubMed][CrossRef]
142. Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, Koblin BA, Buchbinder SP, Keefer MC, Tomaras GD, Frahm N, Hural J, Anude C, Graham BS, Enama ME, Adams E, DeJesus E, Novak RM, Frank I, Bentley C, Ramirez S, Fu R, Koup RA, Mascola JR, Nabel GJ, Montefiori DC, Kublin J, McElrath MJ, Corey L, Gilbert PB, HVTN 505 Study Team. 2013. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med 369:2083–2092. [PubMed][CrossRef]
143. Scott-Algara D, Mancini-Bourgine M, Fontaine H, Pol S, Michel ML. 2010. Changes to the natural killer cell repertoire after therapeutic hepatitis B DNA vaccination. PloS One 5:e8761. doi:10.1371/journal.pone.0008761. [PubMed][CrossRef]
144. Ledgerwood JE, Zephir K, Hu Z, Wei CJ, Chang L, Enama ME, Hendel CS, Sitar S, Bailer RT, Koup RA, Mascola JR, Nabel GJ, Graham BS, VRC 310 Study Team. 2013. Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect. J Infect Dis 208:418–422. [PubMed][CrossRef]
145. Khurana S, Wu J, Dimitrova M, King LR, Manischewitz J, Graham BS, Ledgerwood JE, Golding H. 2013. DNA priming prior to inactivated influenza A(H5N1) vaccination expands the antibody epitope repertoire and increases affinity maturation in a boost-interval-dependent manner in adults. J Infect Dis 208:413–417. [PubMed][CrossRef]
146. 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 282:476–480. [PubMed][CrossRef]
147. Le TP, Coonan KM, Hedstrom RC, Charoenvit Y, Sedegah M, Epstein JE, Kumar S, Wang R, Doolan DL, Maguire JD, Parker SE, Hobart P, Norman J, Hoffman SL. 2000. Safety, tolerability and humoral immune responses after intramuscular administration of a malaria DNA vaccine to healthy adult volunteers. Vaccine 18:1893–1901. [PubMed][CrossRef]
148. McConkey SJ, Reece WH, Moorthy VS, Webster D, Dunachie S, Butcher G, Vuola JM, Blanchard TJ, Gothard P, Watkins K, Hannan CM, Everaere S, Brown K, Kester KE, Cummings J, Williams J, Heppner DG, Pathan A, Flanagan K, Arulanantham N, Roberts MT, Roy M, Smith GL, Schneider J, Peto T, Sinden RE, Gilbert SC, Hill AV. 2003. Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nat Med 9:729–735. [PubMed][CrossRef]
149. Moorthy VS, Pinder M, Reece WH, Watkins K, Atabani S, Hannan C, Bojang K, McAdam KP, Schneider J, Gilbert S, Hill AV. 2003. Safety and immunogenicity of DNA/modified vaccinia virus Ankara malaria vaccination in African adults. J Infect Dis 188:1239–1244. [PubMed][CrossRef]
150. Dunachie SJ, Walther M, Epstein JE, Keating S, Berthoud T, Andrews L, Andersen RF, Bejon P, Goonetilleke N, Poulton I, Webster DP, Butcher G, Watkins K, Sinden RE, Levine GL, Richie TL, Schneider J, Kaslow D, Gilbert SC, Carucci DJ, Hill AV. 2006. A DNA prime-modified vaccinia virus Ankara boost vaccine encoding thrombospondin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge. Infect Immun 74:5933–5942. [PubMed][CrossRef]
151. Wang R, Richie TL, Baraceros MF, Rahardjo N, Gay T, Banania JG, Charoenvit Y, Epstein JE, Luke T, Freilich DA, Norman J, Hoffman SL. 2005. Boosting of DNA vaccine-elicited gamma interferon responses in humans by exposure to malaria parasites. Infect Immun 73:2863–2872. [PubMed][CrossRef]
152. Moorthy VS, Imoukhuede EB, Milligan P, Bojang K, Keating S, Kaye P, Pinder M, Gilbert SC, Walraven G, Greenwood BM, Hill AS. 2004. A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults. PLoS Med 1:e33. doi:10.1371/journal.pmed.0010033. [PubMed][CrossRef]
153. Moorthy VS, Imoukhuede EB, Keating S, Pinder M, Webster D, Skinner MA, Gilbert SC, Walraven G, Hill AV. 2004. Phase 1 evaluation of 3 highly immunogenic prime-boost regimens, including a 12-month reboosting vaccination, for malaria vaccination in Gambian men. J Infect Dis 189:2213–2219. [PubMed][CrossRef]
154. Epstein JE, Charoenvit Y, Kester KE, Wang R, Newcomer R, Fitzpatrick S, Richie TL, Tornieporth N, Heppner DG, Ockenhouse C, Majam V, Holland C, Abot E, Ganeshan H, Berzins M, Jones T, Freydberg CN, Ng J, Norman J, Carucci DJ, Cohen J, Hoffman SL. 2004. Safety, tolerability, and antibody responses in humans after sequential immunization with a PfCSP DNA vaccine followed by the recombinant protein vaccine RTS,S/AS02A. Vaccine 22:1592–1603. [PubMed][CrossRef]
155. Mehendale S, Thakar M, Sahay S, Kumar M, Shete A, Sathyamurthi P, Verma A, Kurle S, Shrotri A, Gilmour J, Goyal R, Dally L, Sayeed E, Zachariah D, Ackland J, Kochhar S, Cox JH, Excler JL, Kumaraswami V, Paranjape R, Ramanathan VD. 2013. Safety and immunogenicity of DNA and MVA HIV-1 subtype C vaccine prime-boost regimens: a phase I randomised trial in HIV-uninfected Indian volunteers. PloS One 8:e55831. doi:10.1371/journal.pone.0055831. [PubMed][CrossRef]
156. Ledgerwood JE, Hu Z, Gordon IJ, Yamshchikov G, Enama ME, Plummer S, Bailer R, Pearce MB, Tumpey TM, Koup RA, Mascola JR, Nabel GJ, Graham BS, VRC 304 and VRC 305 Study Teams. 2012. Influenza virus h5 DNA vaccination is immunogenic by intramuscular and intradermal routes in humans. Clin Vaccine Immunol 19:1792–1797. [PubMed][CrossRef]
157. Kopycinski J, Cheeseman H, Ashraf A, Gill D, Hayes P, Hannaman D, Gilmour J, Cox JH, Vasan S. 2012. A DNA-based candidate HIV vaccine delivered via in vivo electroporation induces CD4 responses toward the alpha4beta7-binding V2 loop of HIV gp120 in healthy volunteers. Clin Vaccine Immunol 19:1557–1559. [PubMed][CrossRef]
158. Kay MA. 2011. State-of-the-art gene-based therapies: the road ahead. Nat Rev Genetics 12:316–328. [PubMed][CrossRef]
159. Moreno S, Lopez-Fuertes L, Vila-Coro AJ, Sack F, Smith CA, Konig SA, Wittig B, Schroff M, Juhls C, Junghans C, Timon M. 2004. DNA immunisation with minimalistic expression constructs. Vaccine 22:1709–1716. [PubMed][CrossRef]
160. Walters AA, Kinnear E, Shattock RJ, McDonald JU, Caproni LJ, Porter N, Tregoning JS. 2014. Comparative analysis of enzymatically produced novel linear DNA constructs with plasmids for use as DNA vaccines. Gene Ther 21:645–652. [PubMed][CrossRef]
161. Cranenburgh RM, Hanak JA, Williams SG, Sherratt DJ. 2001. Escherichia coli strains that allow antibiotic-free plasmid selection and maintenance by repressor titration. Nucleic Acids Res 29:E26. [PubMed][CrossRef]
162. Mairhofer J, Cserjan-Puschmann M, Striedner G, Nobauer K, Razzazi-Fazeli E, Grabherr R. 2010. Marker-free plasmids for gene therapeutic applications: lack of antibiotic resistance gene substantially improves the manufacturing process. J Biotechnol 146:130–137. [PubMed][CrossRef]
163. Vidal L, Pinsach J, Striedner G, Caminal G, Ferrer P. 2008. Development of an antibiotic-free plasmid selection system based on glycine auxotrophy for recombinant protein overproduction in Escherichia coli. J Biotechnol 134:127–136. [PubMed][CrossRef]
164. Szpirer CY, Milinkovitch MC. 2005. Separate-component-stabilization system for protein and DNA production without the use of antibiotics. Biotechniques 38:775–781. [PubMed][CrossRef]
165. Luke J, Carnes AE, Hodgson CP, Williams JA. 2009. Improved antibiotic-free DNA vaccine vectors utilizing a novel RNA based plasmid selection system. Vaccine 27:6454–6459. [PubMed][CrossRef]
166. Goh S, Good L. 2008. Plasmid selection in Escherichia coli using an endogenous essential gene marker. BMC Biotechnol 8:61. [PubMed][CrossRef]
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/content/journal/microbiolspec/10.1128/microbiolspec.PLAS-0028-2014
2014-11-28
2017-09-21

Abstract:

DNA plasmids can be used to induce a protective (or therapeutic) immune response by delivering genes encoding vaccine antigens. That naked DNA (without the refinement of coat proteins or host evasion systems) can cross from outside the cell into the nucleus and be expressed is particularly remarkable given the sophistication of the immune system in preventing infection by pathogens. As a result of the ease, low cost, and speed of custom gene synthesis, DNA vaccines dangle a tantalizing prospect of the next wave of vaccine technology, promising individual designer vaccines for cancer or mass vaccines with a rapid response time to emerging pandemics. There is considerable enthusiasm for the use of DNA vaccination as an approach, but this enthusiasm should be tempered by the successive failures in clinical trials to induce a potent immune response. The technology is evolving with the development of improved delivery systems that increase expression levels, particularly electroporation and the incorporation of genetically encoded adjuvants. This review will introduce some key concepts in the use of DNA plasmids as vaccines, including how the DNA enters the cell and is expressed, how it induces an immune response, and a summary of clinical trials with DNA vaccines. The review also explores the advances being made in vector design, delivery, formulation, and adjuvants to try to realize the promise of this technology for new vaccines. If the immunogenicity and expression barriers can be cracked, then DNA vaccines may offer a step change in mass vaccination.

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TABLE 1

Published DNA vaccine clinical trials.

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0028-2014
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TABLE 2

Novel DNA vaccine technologies to remove antibiotic resistance

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0028-2014

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