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A Blueprint for DNA Vaccine Design

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DNA Vaccines

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1143))

Abstract

Although safety concerns have been overcome, lower immunogenicity profiles of DNA vaccines have hindered their progress in humans. DNA vaccines need to make up for this limitation by altering plasmid construction through vector design innovations intended for enhancement of transgene expression and immunogenicity. The next-generation vectors also address safety issues such as selection markers. This chapter discusses (a) plasmid backbone design, (b) enhancement of antigenic protein expression and immunogenicity, and (c) vector modification to increase innate immunity. Modifications of the basic design, when combined with improved delivery devices and/or prime/boost regimens, may enhance DNA vaccine performance and clinical outcomes.

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References

  1. Kutzler MA, Weiner DB (2008) DNA vaccines: ready for prime time? Nat Rev Genet 9:776–788

    Article  CAS  PubMed  Google Scholar 

  2. Fioretti D, Iurescia S, Rinaldi M (2013) Recent advances in design of immunogenic and effective naked DNA vaccines against cancer. Recent Pat Anticancer Drug Discov 9:66–82

    Google Scholar 

  3. Donnelly JJ, Ulmer JB, Shiver JW et al (1997) DNA vaccines. Annu Rev Immunol 15: 617–648

    Article  CAS  PubMed  Google Scholar 

  4. 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 90:4455–4459

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Manthorpe M, Cornefert-Jensen F, Hartikka J et al (1993) Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Hum Gene Ther 4:419–431

    Article  CAS  PubMed  Google Scholar 

  6. Cazeaux N, Bennasser Y, Vidal PL et al (2002) Comparative study of immune responses induced after immunization with plasmids encoding the HIV-1 Nef protein under the control of the CMV-IE or the muscle-specific desmin promoter. Vaccine 20:3322–3331

    Article  CAS  PubMed  Google Scholar 

  7. Luke JM, Vincent JM, Du SX et al (2011) Improved antibiotic-free plasmid vector design by incorporation of transient expression enhancers. Gene Ther 18:334–343

    Article  CAS  PubMed  Google Scholar 

  8. Barouch DH, Yang ZY, Kong WP et al (2005) A human T-cell leukemia virus type 1 regulatory element enhances the immunogenicity of human immunodeficiency virus type 1 DNA vaccines in mice and nonhuman primates. J Virol 79:8828–8834

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Li C, Goudy K, Hirsch M et al (2009) Cellular immune response to cryptic epitopes during therapeutic gene transfer. Proc Natl Acad Sci USA 106:10770–10774

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Williams JAV (2013) Vector design for improved DNA vaccine efficacy, safety and production. Vaccine 1:225–249

    Article  Google Scholar 

  11. EMA (2007) Presence of the antibiotic resistance marker gene nptII in GM plants for food and feed uses. Vol EMEA/CVMP/56937/2007

    Google Scholar 

  12. Oliveira PH, Mairhofer J (2013) Marker-free plasmids for biotechnological applications: implications and perspectives. Trends Biotechnol 31:539–547

    Article  CAS  PubMed  Google Scholar 

  13. Schleef M (2013) Minicircle and miniplasmid DNA vectors: the future of nonviral and viral gene transfer. Wiley, Weinheim

    Book  Google Scholar 

  14. Osborn MJ, McElmurry RT, Lees CJ et al (2011) Minicircle DNA-based gene therapy coupled with immune modulation permits long-term expression of alpha-l-iduronidase in mice with mucopolysaccharidosis type I. Mol Ther 19:450–460

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Narsinh KH, Jia F, Robbins RC et al (2011) Generation of adult human induced pluripotent stem cells using nonviral minicircle DNA vectors. Nat Protoc 6:78–88

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Andre S, Seed B, Eberle J et al (1998) Increased immune response elicited by DNA vaccination with a synthetic gp120 sequence with optimized codon usage. J Virol 72: 1497–1503

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Fath S, Bauer AP, Liss M et al (2011) Multiparameter RNA and codon optimization: a standardized tool to assess and enhance autologous mammalian gene expression. PLoS One 6:e17596

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Weide B, Garbe C, Rammensee HG et al (2008) Plasmid DNA- and messenger RNA-based anti-cancer vaccination. Immunol Lett 115:33–42

    Article  CAS  PubMed  Google Scholar 

  19. Williams JA, Carnes AE, Hodgson CP (2009) Plasmid DNA vaccine vector design: impact on efficacy, safety and upstream production. Biotechnol Adv 27:353–370

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Laddy DJ, Yan J, Kutzler M et al (2008) Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens. PLoS One 3:e2517

    Article  PubMed Central  PubMed  Google Scholar 

  21. Rinaldi M, Fioretti D, Iurescia S et al (2008) Anti-tumor immunity induced by CDR3-based DNA vaccination in a murine B-cell lymphoma model. Biochem Biophys Res Commun 370: 279–284

    Article  CAS  PubMed  Google Scholar 

  22. Lam AP, Dean DA (2010) Progress and prospects: nuclear import of nonviral vectors. Gene Ther 17:439–447

    Article  CAS  PubMed  Google Scholar 

  23. Conese M, Auriche C, Ascenzioni F (2004) Gene therapy progress and prospects: episomally maintained self-replicating systems. Gene Ther 11:1735–1741

    Article  CAS  PubMed  Google Scholar 

  24. Argyros O, Wong SP, Fedonidis C et al (2011) Development of S/MAR minicircles for enhanced and persistent transgene expression in the mouse liver. J Mol Med (Berl) 89: 515–529

    Article  CAS  Google Scholar 

  25. Coban C, Koyama S, Takeshita F et al (2008) Molecular and cellular mechanisms of DNA vaccines. Hum Vaccin 4:453–456

    Article  CAS  PubMed  Google Scholar 

  26. Desmet CJ, Ishii KJ (2012) Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol 12:479–491

    Article  CAS  PubMed  Google Scholar 

  27. O’Neill LA (2013) Immunology. Sensing the dark side of DNA. Science 339:763–764

    Article  PubMed  Google Scholar 

  28. Loo YM, Gale M Jr (2011) Immune signaling by RIG-I-like receptors. Immunity 34:680–692

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Babiuk S, Mookherjee N, Pontarollo R et al (2004) TLR9−/− and TLR9+/+ mice display similar immune responses to a DNA vaccine. Immunology 113:114–120

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Ishii KJ, Kawagoe T, Koyama S et al (2008) TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Nature 451:725–729

    Article  CAS  PubMed  Google Scholar 

  31. Kobiyama K, Jounai N, Aoshi T, Tozuka M, Takeshita F, Coban C, Ishii KJ (2013) Innate immune signaling by, and genetic adjuvants for DNA vaccination. Vaccine 1:278–292

    Article  Google Scholar 

  32. Coban C, Kobiyama K, Aoshi T et al (2011) Novel strategies to improve DNA vaccine immunogenicity. Curr Gene Ther 11: 479–484

    Article  CAS  PubMed  Google Scholar 

  33. Li L, Saade F, Petrovsky N (2012) The future of human DNA vaccines. J Biotechnol 162:171–182

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Sandhu KS, Pandey S, Maiti S et al (2008) GASCO: genetic algorithm simulation for codon optimization. In Silico Biol 8:187–192

    CAS  PubMed  Google Scholar 

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Author notes

    Authors and Affiliations

    1. Section of Medical Biotechnology, Institute of Translational Pharmacology (IFT), National Research Council (CNR), via Fosso del Cavaliere 100, 00133, Rome, Italy

      Sandra Iurescia, Daniela Fioretti & Monica Rinaldi

    Authors
    1. Sandra Iurescia
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    2. Daniela Fioretti
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    3. Monica Rinaldi
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    Corresponding author

    Correspondence to Monica Rinaldi .

    Editor information

    Editors and Affiliations

    1. Section Of Medical Biotechnology, Institute of Translational Pharmacology (IFT), National Research Council (CNR), Rome, Italy

      Monica Rinaldi

    2. Section Of Medical Biotechnology, Institute of Translational Pharmacology (IFT), National Research Council (CNR), Rome, Italy

      Daniela Fioretti

    3. Section Of Medical Biotechnology, Institute of Translational Pharmacology (IFT), National Research Council (CNR), Rome, Italy

      Sandra Iurescia

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    © 2014 Springer Science+Business Media New York

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    Iurescia, S., Fioretti, D., Rinaldi, M. (2014). A Blueprint for DNA Vaccine Design. In: Rinaldi, M., Fioretti, D., Iurescia, S. (eds) DNA Vaccines. Methods in Molecular Biology, vol 1143. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0410-5_1

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    • DOI: https://doi.org/10.1007/978-1-4939-0410-5_1

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    • Publisher Name: Humana Press, New York, NY

    • Print ISBN: 978-1-4939-0409-9

    • Online ISBN: 978-1-4939-0410-5

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