Springer Seminars in Immunopathology

, Volume 19, Issue 2, pp 223–232 | Cite as

Gene immunization for allergic disorders

  • Mark Roman
  • Hans L. Spiegelberg
  • David Broide
  • Eyal Razz


For immunotherapy to regain a major role as a treatment for allergic disorders, improvements in current allergen immunotherapy are needed to decrease treatment-associated risks when compared to the risks involved in current pharmacological management protocols [1]. The recent findings described in this review suggest that there is potential for the development of a novel form of immunotherapy, i.e., allergen gene vaccination, which would be safe and effective. Gene vaccination does not result in inflammation when injected 11.d and has been shown to down-regulate antigen-specific IgE antibodies in mice and rats, and in the reduction of late phase allergic responses. The presence of ISS-containing DNA in the vaccine formulation, whether within the pDNA expression vectors, or co-injected, is important in the induction of IFN-γ-mediated Th1 cell differentiation, IL-5 inhibition, and B cell isotype switching, which cumulatively may lead to the reduction of allergic responses (Fig. 4).

To date, all the in vivo experiments showing IgE inhibition have been performed in mice and rats. However, based on the combined observations that pDNA is also taken up by human skin cells transplanted onto nude mice [25], and that ISS-containing DNA induces Th1-promoting cytokines from human PBMC, it is possible that the antiallergic responses observed in rodents will also occur in human. As for safety considerations, in vitro data indicate that the transfected cells secrete low levels of antigen which are unlikely to induce the anaphylactic reactions seen in vivo with classical immunotherapy. Furthermore, the allergens encoded by pDNA constructs can be designed to include a transmembrane domain and anchor, thereby preventing the secretion of allergen and possible induction of anaphylactic reactions.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mygind N, Dahl R, Pederson S, Thestrup-Pederson K (1996) Essential allergy, 2nd edn. Blackwell OxfordGoogle Scholar
  2. 2.
    Frigas E, Motojima S, Gleich GJ (1991) The eosinophilic injury to the mucosa of the airways in the pathogenesis of bronchial asthma. Eur Respir J [Suppl] 13: 123sGoogle Scholar
  3. 3.
    Adkinson NF, Eggleston PA, Eney D, Goldstein EO, Schuberth KC, Bacon JR, Hamilton RG, Weiss ME, Arshad H, Meinert CL, Tanascia J, Wheeler B (1997) A controlled trial of immunotherapy for asthma in allergic children. N Engl J Med 336: 324PubMedGoogle Scholar
  4. 4.
    Raz E, Carson DA, Parker SE, Parr TB, Abai AM, Aichinger G, Gromkowski SH, Singh M, Lew D, Yankauckas MA, Baird S, 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: 9519PubMedGoogle Scholar
  5. 5.
    Raz E, Tighe H, Sato Y, Corr MP, 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: 5141PubMedGoogle Scholar
  6. 6.
    Broide D, Orozco EM, Roman M, Carson DA, Raz E (1997) Intradermal gene vaccination down-regulates both arms of the allergic response. J Allergy Clin Immunol 99: S129Google Scholar
  7. 7.
    Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Randall-Deck RR, DeWitt CM, Friedman A, Hawe LA, Leander KR, Martinez D, Perry HC, Shiver JW, Montgomery DL, Liu MA (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259: 1745PubMedGoogle Scholar
  8. 8.
    Mosmann TR, Coffman RL (1989) The Th1 and Th2 cells: differrent patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7: 145–173PubMedGoogle Scholar
  9. 9.
    Coffman RL, Carty J (1985) A T cell activity that enhances polyclonal IgE production and its inhibition by iinterferon-γ. J Immunol 136: 949Google Scholar
  10. 10.
    Snapper CM, Paul WE (1987) Interferon-γ and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science 236:944PubMedGoogle Scholar
  11. 11.
    Parronchi P, Macchia D, Piccini MP, Biswas P, Simonelli C, Maggi E, Ricci M, Ansari AA, Romagnani S (1991) Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. Proc Natl Acad Sci USA 88:4538PubMedGoogle Scholar
  12. 12.
    Wierenga EA, Snock M, Groot C de, Chretien I, Bos JD, Jansen HM, Kapsenberg M (1990) Evidence for compartmentalization of functional subsets of CD4+ T lymphocytes in atopic patients. J Immunol 144:4651–4656PubMedGoogle Scholar
  13. 13.
    Coutelier JP, Logt JTM van der, Heessen WA, Waamer G, van-Snick J (1987) IgG2a restriction of murine antibodies elicited by viral infections. J Exp Med 165:2373Google Scholar
  14. 14.
    Beck L, Spiegelberg HL (1989) The polyclonal and antigen-specific IgE and IgG subclass response of mice injected with ovalbumin in alum or complete Freund's adjuvant. Cell Immunol 123:1PubMedGoogle Scholar
  15. 15.
    Hsu CH, Chua KY, Tao MH, Lai YL, Wu HD, Huang SK, Hsieh KH (1996) Immunoprophylaxis of allergen-induced immunoglobulin E synthesis and airway hyper responsiveness in vivo by genetic immunization. Nature Med 2:540PubMedGoogle Scholar
  16. 16.
    Slater JE, Zhang YJ, Athur-Smith A, Colberg-Poley A (1997) A DNA vaccine inhibits IgE responses to the latex allergen Hev b 5 in mice. J Allergy Clin Immunol 99:S504Google Scholar
  17. 17.
    Sato Y, Roman M, Tighe H, Lee D, Corr MP, Nguyen MD, Silverman GJ, Lotz M, Carson DA, Raz E (1996) Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science 273:352Google Scholar
  18. 18.
    Yamamoto S, Yamamoto T, Kataoka T, Kuramoto E, Yano O, Tokunaga T (1992) Unique palindromic sequences in sythetic oligonucleotides are required to induce IFN and IFN-mediated natural killer aactivity. J Immunol 148:4072–4076PubMedGoogle Scholar
  19. 19.
    Klinman DM, Yi AK, Beaucage SL, Conover J, Krieg AM (1996) CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon γ. Proc Natl Acad Sci USA 93:2879PubMedGoogle Scholar
  20. 20.
    Raz E, Roman M, Orozco EM, Carson DA (1997) Immunostimulatory DNA sequences (ISS) are a ThI promoting adjuvant. J Allergy Clin Immunol 99:S365Google Scholar
  21. 21.
    Roman M, Orozco EM, Goodman J, Nguyen MD, Sato Y, Ronaghy A, Kombluth RS, Richman DD, Carson DA, Raz E (1997) Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat Med 3:849–854PubMedGoogle Scholar
  22. 22.
    Cowdery JS, Chace JH, Yi AK, Krieg AM (1996) Bacterial DNA induces NK cells to produce IFN-gamma in vivo and increases the toxicity of lipopolysaccharides. J Immunol 156:4570PubMedGoogle Scholar
  23. 23.
    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 374:546CrossRefPubMedGoogle Scholar
  24. 24.
    Liang H, Nishioka Y, Reich CF, Pisetsky DS, Lipsky PE (1996) Activation of human B cells by phospborothioate oligodeoxynucleotides. J Clin Invest 98:1119PubMedGoogle Scholar
  25. 25.
    Hengge UR, Walker PS, Vogel JC (1996) Expression of naked DNA in human, pig, and mouse skin. J Clin Invest 97:2911PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • Mark Roman
    • 1
  • Hans L. Spiegelberg
    • 3
  • David Broide
    • 2
  • Eyal Razz
    • 2
  1. 1.Dynavax Technologies CorporationSan DiegoUSA
  2. 2.Department of MedicineUniversity of California San Diego, School of MedicineCALa JollaUSA
  3. 3.Department of PediatricsUniversity of California San Diego, School of MedicineLa JollaUSA

Personalised recommendations