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DNA Vaccines

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Vaccine Protocols

Part of the book series: Methods in Molecular Medicineā„¢ ((MIMM,volume 4))

Abstract

The use of DNA and mRNA as vectors for immunization is a relatively recent development in the field of vaccines. The first paper demonstrating the efficacy of a DNA vaccine in an animal model of viral disease was published in 1993 (1). The rationale for using nucleic acids as vaccines came from the Initial observations that mtramuscular (im) injection of nonrephcating plasmid DNA expression vectors or mFWA-encoding reporter genes could result in the in vivo expression of proteins in mouse muscle cells (2). This ability to express proteins in vivo offers the opportunity to generate immune responses against foreign antigens encoded by the nucleic acid. In addition, both humoral and cell-mediated immune (CMI) responses, such as cytotoxic T-lymphocytes (CTL), can be induced. In general, CTL responses require endogenous expression of the antigen, such as during immunization with live viruses or replicating vectors, whereas subunit protein, polysaccharide conjugate, or inactivated virus vaccines generate humoral immune responses, but not CTL. Therefore, the technique of DNA injection has potential advantages over certain other vaccine technologies.

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References

  1. Ulmer, J. B., Donnelly, J. J., Parker, S. E., Rhodes, G. H., Felgner, P. L., Dwarki, V. J., Gromkowski, S. H., Deck, R. R., Dewitt, C. M., Friedman, A., Hawe, L.A., Leander, K. R., Martinez, D., Perry, H. C., Shiver, J. W., Montgomery, D. L.,and Liu, M.A. (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259, 1745ā€“1749.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  2. Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., and Felgner, P L. (1990) Direct gene transfer into mouse muscle in vivo. Science 247, 1465ā€“1468.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  3. Ulmer, J. B., Donnelly, J. J., and Liu, M. A. (1994) Vaccination with polynucleotrdes: a novel means of generating immunity, in New Vaccinology (Kurstak, E., ed.), Plenum Medical, New York, pp. 13ā€“22.

    Google ScholarĀ 

  4. Robmson, H. L., Hunt, L. A., and Webster, R. G. (1993) Protection against a lethal influenza virus challenge by immunization with a haemagglutmm-expressing plasmid DNA. Vaccine 11, 957ā€“960.

    ArticleĀ  Google ScholarĀ 

  5. Montgomery, D. L., Shiver, J. W., Leander, K. R., Perry, H. C., Friedman, A., Martmez, D., Ulmer, J. B., Donnelly, J. J., and Liu, M. A. (1993) Heterologous and homologous protection against influenza A by DNA vaccination: optimization of DNA vectors. DNA CellBiol 12, 777ā€“783.

    ArticleĀ  CASĀ  Google ScholarĀ 

  6. Cox, G. J. M., Zamb, T. J., and Babmk, L. A. (1993) Bovine Herpesvirus 1: immune responses in mice and cattle iqected with plasmid DNA. J Virol 67, 5664ā€“5667.

    PubMedĀ  CASĀ  Google ScholarĀ 

  7. Xiang, Z. Q., Spitalmk, S., Tran, M., Wunner, W. H., Cheng, J., and Ertl, H. C. J. (1994) Vaccmation with a plasmid vector carrying the rabies virus glycoprotem gene induces protective immunity against rabies vuus. Virology 199, 132ā€“140.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  8. Sedegah, M., Hedstrom, R., Hobart, P., and Hoffman, S. L. (1994) Protection against malaria by immunization with circumsporozoite protein plasmrd DNA. Proc. Natl. Acad. Sci. USA 91, 9866ā€“9870.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  9. Xu, D. and Liew, F. Y. (1994) Genetic vaccination against leishmaniasis Vaccine 12, 1534ā€“1536.

    CASĀ  Google ScholarĀ 

  10. Ulmer, J. B, Lm, M. A., Montgomery, D. L., Yawman, A. M, Drowart, A., Dems, O., et al. (1996) Immunogemcity and efficacy of a tuberculosis DNA vaccme, in Vaccines 96 (Chanock, R., Brown, F., Gmsberg, M., and Novby, E., eds), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, in press.

    Google ScholarĀ 

  11. Wang, B., Ugen, K. E., Srikantan, V., Agadjanyan, M. G., Dang, K., Refaeh, Y., Sato, A. I., Boyer, J., Williams, W. V, and Werner, D. B. (1993) Gene maculation generates immune responses against human immunodeficiency virus type 1. Proc. Natl. Acad Sci. USA 90, 41564160.

    Google ScholarĀ 

  12. Wang, B., Boyer, J., Srikantan, V., Coney, L., Carrano, R., Phan, C., Merva, M, Dang, K., Agadjanyan, M., Gilbert, L., Ugen, K. E., Williams, W. V., and Weiner, D.B (1993) DNA inoculation induces neutralizing immune responses against human nnmunodeficiency virus type 1 in mice and nonhuman primates. DNA Cell Biol. 12, 799ā€“805.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  13. Davis, H. L., Michel, M.-L, and Whalen, R. G. (1993) DNA-based inmunization induces continuous secretion of hepatitis B surface antigen and high levels of circulating anttbody. Hum. Mol. Genet. 2, 1847ā€“1851.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  14. Corny, R. M., LoBuglio, A. F., Kantor, J., Schlom, J., Loechel, F., Moore, S. E, Sumerel, L. A., Barlow, D. L., Abrams, S., and Carrel, D. T (1994) Immune response to a carcinoembryonic antigen polynucleotide vaccme. Cancer Res. 54, 116ā€“1168

    Google ScholarĀ 

  15. Geissler, E. K., Wang, J., Fechner, J. H., Burlingham, W. J, and Knechtle, S J (1993) Immunity to MHC Class I antigen following direct DNA transfer into skeletal muscle. J. Immunol. 152, 413ā€“421.

    Google ScholarĀ 

  16. Wahl, W. L., Plautz, G. E., Fox, B. A., Nabel, G. J., Shu, S., and Chang, A. E. (1992) Generation of therapeutic T lymphocytes after in vivo transfection of tumor with a gene encoding allogenerc Class I Major Histocompatibihty Complex antigen. Surg. Forum 43, 47ā€“78.

    Google ScholarĀ 

  17. Hawkms, R. E., Wmter, G., Hamblin, T. J., Stevenson, F. K., and Russell, S. J. (1993) A genetic approach to idiotyprc vaccination. J. Immunotherapy 14, 273ā€“278.

    ArticleĀ  Google ScholarĀ 

  18. Wolff, J. A., Dowty, M. E., Jiao, S., Repetto, G., Berg, R. K., Ludtke, J. J., Williams, P., and Slautterback, D. B. (1992) Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammahan skeletal muscle. J. Cell Sci. 103, 1249ā€“1259.

    PubMedĀ  CASĀ  Google ScholarĀ 

  19. Sambrook, J., Fritsch, E. F., and Mamatis, T. (1989) Molecular Cloning: A Laboratory Manual, 2nd ed. (Nolan, C., ed.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

    Google ScholarĀ 

  20. Wells, D. J. (1993) Improved gene transfer by direct plasmid injection associated with regeneration in mouse skeletal muscle FEBSLett. 332, 179ā€“182.

    ArticleĀ  CASĀ  Google ScholarĀ 

  21. Davis, H. L., Whalen, R. G., and Demeneix, B. A. (1993) Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Hum. Gene Ther. 4, 151ā€“159.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  22. Vitadello, M., Schiaffino, M. V., Picard, A., Scarpa, M., and Schiaffino, S. (1994) Gene transfer in regenerating muscle. Hum. Gene Ther. 5, 11ā€“18.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  23. Wolff, J. A., Williams, P., Acsadi, G., Jiao, S., Jam, G, and Chong, W. (1991) Conditions affecting direct gene transfer into rodent muscle in vivo. Blotechnzques 11, 474ā€“485.

    CASĀ  Google ScholarĀ 

  24. Manthorpe, M., Conrefert-Jensen, F., Hartikka, J., Felgner, J., Rundell, A., Margahth, M., and Dwarkt, V. J. (1993) Gene therapy by mtramuscular mjecuon of plasnud DNA: studies on fnefly luciferase gene expression in mice. Hum. Gene Ther. 4, 419ā€“431.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  25. Williams, R. S., Johnston, S. A., Riedy, M, Devit, M. J., McElhgott, S G., and Sanford, J. C. (1991) Introduction of foreign genes into tissues of hving mice by DNA-coated microprojectiles. Proc Natl. Acad. Sci. USA 88, 2726ā€“2730

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  26. Tang, D. C., Devit, M., and Johnston, S. A. (1992) Genetic mnnumzation is a simple method for eliciting an immune response. Nature 356, 152ā€“154.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  27. Fynan, E. F., Webster, R. G., Fuller, D. H., Haynes, J. R., Santoro, J. C., and Robinson, H. L. (1993) DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Natl. Acad. Sci. USA 90, 11,478ā€“11,482.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  28. Yankaukas, M. A., Morrow, J. E., Parker, S. E., Abai, A., Rhodes, G. H., Dwarki, V. J., and Gromkowski, S. H. (1993) Long-term anti-nucleoprotem cellular and humoral nnmunity is induced by intramuscular inJection of plasmid DNA containing gene. DNA Cell Biol. 12, 771ā€“776.

    ArticleĀ  Google ScholarĀ 

  29. Ulmer, J. B., Deck, R. R., Dewitt, C. M., Friedman, A., Donnelly, J. J., and Liu, M. A. (1994) Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines. Vaccine 12, 1541ā€“1544.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  30. Okuda, K., Bukawa, H., Hamajima, K., Kawamoto, S., Sekigawa, K.-I., Yamada, Y., et al. (1995) Induction of potent humoral and cell mediated immune responses following direct injection of DNA encoding the HIV type I env and rev gene products. AIDS Res. Hum. Retrovir. 11, 933ā€“943.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  31. Hui, K. M., Sabapathy, T. K., Oei, A., and Chia, T. F. (1994) Generation of alloreacttve cytotoxic T lymphocytes by particle bombardment-mediated gene transfer. J. Immunol. Methods 171, 147ā€“155.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  32. Cheng, L., Ziegelhoffer, P. R., and Yang, N.-S. (1993) In vivo promoter activity and transgene expression in mammalian somatic tissues evaluated by using particle bombardment. Proc. Natl. Acad. Scr USA 90, 4455ā€“4459.

    ArticleĀ  CASĀ  Google ScholarĀ 

  33. Greenfield, L., Simpson, L., and Kaplan, D. (1975) Conversion of closed circular DNA molecules to single-nicked molecules by digestion with DNAase I in the presence of ethidium bromide. Biochzm. Bzophys. Acta 407, 365ā€“374.

    CASĀ  Google ScholarĀ 

  34. Stribling, R., Brunette, E., Liggitt, D., Gaensler, K., and Debs, R. (1992) Aerosol gene delivery in vivo. Proc. Natl. Acad. Sci. USA 89, 11,277ā€“11,281.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  35. Philip, R., Liggitt, D., Philip, M., Dazin, P., and Debs, R. (1993) In vivo gene delivery: efficient transfection of T lymphocytes in adult mice. J. Biol. Chem. 268, 16,087ā€“16,090.

    PubMedĀ  CASĀ  Google ScholarĀ 

  36. Zhu, N., Liggit, D., Lm, Y., and Debs, R. (1993) Systemic gene expression after intravenous DNA delivery into adult mice. Sczence 261, 209ā€“211.

    ArticleĀ  CASĀ  Google ScholarĀ 

  37. Raz, E., Carson, D. A., Parker, S. E, Parr, T. B., Abai, A. M., Aichmger, G., Gromkowski, S. H., Singh, M., Lew, D., Yankauckas, M. E., Baird, S. M., and Rhodes, G. R. (1994) Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc. Natl. Acad. Sci. USA 91, 9519ā€“9523

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

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Ā© 1996 Humana Press Inc, Totowa, NJ

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Ulmer, J.B., Montgomery, D.L., Donnelly, J.J., Liu, M.A. (1996). DNA Vaccines. In: Robinson, A., Farrar, G.H., Wiblin, C.N. (eds) Vaccine Protocols. Methods in Molecular Medicineā„¢, vol 4. Humana Press. https://doi.org/10.1385/0-89603-334-1:289

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  • DOI: https://doi.org/10.1385/0-89603-334-1:289

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-334-4

  • Online ISBN: 978-1-59259-588-4

  • eBook Packages: Springer Protocols

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