Skip to main content
SpringerLink
Log in

DNA and RNA Vaccines for Prophylactic and Therapeutic Treatment of Type I Allergy

  • Chapter
  • First Online:
Book cover Gene Vaccines

Abstract

The constant rise in allergies in Western industrialized countries has fueled efforts to develop novel therapies to treat the immunological cause of disease rather than merely ameliorating symptoms. Gene vaccines against allergic diseases may be an attractive alternative to classical specific immunotherapy (SIT) avoiding its pitfalls such as potential side effects as well as low patient compliance. While SIT is commonly believed to rely on the generation of regulatory immune reactions and blocking antibodies, gene based allergy vaccines rather exert immune deviation by balancing allergic TH2 reactions through the generation of allergen specific TH1 cells. In contrast to SIT, gene based allergy vaccines may also have a high potential for prophylactic applications. Already small amounts of translated allergen in the context of DNA/RNA vaccine-inherent danger signals prime a milieu that counteracts the induction of allergic immune responses. Such prophylactic vaccines may very well resemble naturally acquired protection from allergy as it is observed in individuals exposed to microbial compounds during early childhood (hygiene hypothesis). In this chapter, we will discuss different types of DNA vaccines that have been designed to prevent from allergy, and the potential safety hazards associated with their application for prophylactic vaccination of children. Furthermore, we will demonstrate that RNA vaccines are as effective as DNA vaccines, yet with a much higher safety profile, thus making them the most promising candidates for prophylactic vaccination against allergic diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ball T, Sperr WR, Valent P, Lidholm J, Spitzauer S, Ebner C, Kraft D, Valenta R (1999) Induction of antibody responses to new B cell epitopes indicates vaccination character of allergen immunotherapy. Eur J Immunol 29(6):2026–2036

    Article  PubMed  CAS  Google Scholar 

  • Bauer R, Himly M, Dedic A, Ferreira F, Thalhamer J, Hartl A (2003) Optimization of codon usage is required for effective genetic immunization against Art v 1, the major allergen of mugwort pollen. Allergy 58(10):1003–1010

    Article  PubMed  CAS  Google Scholar 

  • Bauer R, Scheiblhofer S, Kern K, Gruber C, Stepanoska T, Thalhamer T, Hauser-Kronberger C, Alinger B, Zoegg T, Gabler M, Ferreira F, Hartl A, Thalhamer J, Weiss R (2006) Generation of hypoallergenic DNA vaccines by forced ubiquitination: preventive and therapeutic effects in a mouse model of allergy. J Allergy Clin Immunol 118(1):269–276

    Article  PubMed  CAS  Google Scholar 

  • Bonifaz LC, Arzate S, Moreno J (1999) Endogenous and exogenous forms of the same antigen are processed from different pools to bind MHC class II molecules in endocytic compartments. Eur J Immunol 29(1):119–131

    Article  PubMed  CAS  Google Scholar 

  • Braun-Fahrlander C, Gassner M, Grize L, Neu U, Sennhauser FH, Varonier HS, Vuille JC, Wuthrich B (1999) Prevalence of hay fever and allergic sensitization in farmer’s children and their peers living in the same rural community. SCARPOL team. Swiss study on childhood allergy and respiratory symptoms with respect to air pollution. Clin Exp Allergy 29(1):28–34

    Article  PubMed  CAS  Google Scholar 

  • Braun-Fahrlander C, Riedler J, Herz U, Eder W, Waser M, Grize L, Maisch S, Carr D, Gerlach F, Bufe A, Lauener RP, Schierl R, Renz H, Nowak D, von Mutius E (2002) Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 347(12):869–877

    Article  PubMed  Google Scholar 

  • Bullens DM, De Swerdt A, Dilissen E, Kasran A, Kroczek RA, Cadot P, Casaer P, Ceuppens JL (2005) House dust mite-specific T cells in healthy non-atopic children. Clin Exp Allergy 35(12):1535–1541

    Article  PubMed  CAS  Google Scholar 

  • Carralot JP, Probst J, Hoerr I, Scheel B, Teufel R, Jung G, Rammensee HG, Pascolo S (2004) Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines. Cell Mol Life Sci 61(18):2418–2424

    Article  PubMed  CAS  Google Scholar 

  • Cheng WF, Hung CF, Hsu KF, Chai CY, He L, Ling M, Slater LA, Roden RB, Wu TC (2001) Enhancement of sindbis virus self-replicating RNA vaccine potency by targeting antigen to endosomal/lysosomal compartments. Hum Gene Ther 12(3):235–252

    Article  PubMed  CAS  Google Scholar 

  • Dobano C, Rogers WO, Gowda K, Doolan DL (2007) Targeting antigen to MHC class I and class II antigen presentation pathways for malaria DNA vaccines. Immunol Lett 111(2):92–102

    Article  PubMed  CAS  Google Scholar 

  • Ege MJ, Bieli C, Frei R, van Strien RT, Riedler J, Ublagger E, Schram-Bijkerk D, Brunekreef B, van Hage M, Scheynius A, Pershagen G, Benz MR, Lauener R, von Mutius E, Braun-Fahrlander C (2006) Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. J Allergy Clin Immunol 117(4):817–823

    Article  PubMed  Google Scholar 

  • Ege MJ, Frei R, Bieli C, Schram-Bijkerk D, Waser M, Benz MR, Weiss G, Nyberg F, van Hage M, Pershagen G, Brunekreef B, Riedler J, Lauener R, Braun-Fahrlander C, von Mutius E (2007) Not all farming environments protect against the development of asthma and wheeze in children. J Allergy Clin Immunol 119(5):1140–1147

    Article  PubMed  Google Scholar 

  • Floistrup H, Swartz J, Bergstrom A, Alm JS, Scheynius A, van Hage M, Waser M, Braun-Fahrlander C, Schram-Bijkerk D, Huber M, Zutavern A, von Mutius E, Ublagger E, Riedler J, Michaels KB, Pershagen G (2006) Allergic disease and sensitization in Steiner school children. J Allergy Clin Immunol 117(1):59–66

    Article  PubMed  Google Scholar 

  • Gabler M, Scheiblhofer S, Kern K, Leitner WW, Stoecklinger A, Hauser-Kronberger C, Alinger B, Lechner B, Prinz M, Vrtala S, Valenta R, Thalhamer J, Weiss R (2006) Immunization with a low-dose replicon DNA vaccine encoding Phl p 5 effectively prevents allergic sensitization. J Allergy Clin Immunol 118(3):734–741

    Article  PubMed  CAS  Google Scholar 

  • Hartl A, Kiesslich J, Weiss R, Bernhaupt A, Mostbock S, Scheiblhofer S, Ebner C, Ferreira F, Thalhamer J (1999a) Immune responses after immunization with plasmid DNA encoding Bet v 1, the major allergen of birch pollen. J Allergy Clin Immunol 103(1 Pt 1):107–113

    Article  PubMed  CAS  Google Scholar 

  • Hartl A, Kiesslich J, Weiss R, Bernhaupt A, Mostbock S, Scheiblhofer S, Flockner H, Sippl M, Ebner C, Ferreira F, Thalhamer J (1999b) Isoforms of the major allergen of birch pollen induce different immune responses after genetic immunization. Int Arch Allergy Immunol 120(1):17–29

    Article  PubMed  CAS  Google Scholar 

  • Hartl A, Hochreiter R, Stepanoska T, Ferreira F, Thalhamer J (2004) Characterization of the protective and therapeutic efficiency of a DNA vaccine encoding the major birch pollen allergen Bet v 1a. Allergy 59(1):65–73

    Article  PubMed  CAS  Google Scholar 

  • Hochreiter R, Stepanoska T, Ferreira F, Valenta R, Vrtala S, Thalhamer J, Hartl A (2003) Prevention of allergen-specific IgE production and suppression of an established Th2-type response by immunization with DNA encoding hypoallergenic allergen derivatives of Bet v 1, the major birch-pollen allergen. Eur J Immunol 33(6):1667–1676

    Article  PubMed  CAS  Google Scholar 

  • 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(5):540–544

    Article  PubMed  CAS  Google Scholar 

  • Jacquet A, Magi M, Haumont M, Jurado M, Garcia L, Bollen A (2003) Absence of immunoglobulin E synthesis and airway eosinophilia by vaccination with plasmid DNA encoding ProDer p 1. Clin Exp Allergy 33(2):218–225

    Article  PubMed  CAS  Google Scholar 

  • Kim TW, Hung CF, Boyd D, Juang J, He L, Kim JW, Hardwick JM, Wu TC (2003) Enhancing DNA vaccine potency by combining a strategy to prolong dendritic cell life with intracellular targeting strategies. J Immunol 171(6):2970–2976

    PubMed  CAS  Google Scholar 

  • Kulig M, Bergmann R, Niggemann B, Burow G, Wahn U (1998) Prediction of sensitization to inhalant allergens in childhood: evaluating family history, atopic dermatitis and sensitization to food allergens. The MAS study group. Multicentre allergy study. Clin Exp Allergy 28(11):1397–1403

    Article  PubMed  CAS  Google Scholar 

  • Lauener RP, Birchler T, Adamski J, Braun-Fahrlander C, Bufe A, Herz U, von Mutius E, Nowak D, Riedler J, Waser M, Sennhauser FH (2002) Expression of CD14 and toll-like receptor 2 in farmers’ and non-farmers’ children. Lancet 360(9331):465–466

    Article  PubMed  CAS  Google Scholar 

  • Lich JD, Elliott JF, Blum JS (2000) Cytoplasmic processing is a prerequisite for presentation of an endogenous antigen by major histocompatibility complex class II proteins. J Exp Med 191(9):1513–1524

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Raviprakash K, Leao IC, Chikhlikar PR, Ewing D, Anwar A, Chougnet C, Murphy G, Hayes CG, August TJ, Marques ET Jr (2003) Dengue 2 PreM-E/LAMP chimera targeted to the MHC class II compartment elicits long-lasting neutralizing antibodies. Vaccine 21(17–18):2178–2189

    Article  PubMed  CAS  Google Scholar 

  • Marenholz I, Kerscher T, Bauerfeind A, Esparza-Gordillo J, Nickel R, Keil T, Lau S, Rohde K, Wahn U, Lee YA (2009) An interaction between filaggrin mutations and early food sensitization improves the prediction of childhood asthma. J Allergy Clin Immunol 123(4):911–916

    Article  PubMed  CAS  Google Scholar 

  • Marques ET Jr, Chikhlikar P, de Arruda LB, Leao IC, Lu Y, Wong J, Chen JS, Byrne B, August JT (2003) HIV-1 p55Gag encoded in the lysosome-associated membrane protein-1 as a DNA plasmid vaccine chimera is highly expressed, traffics to the major histocompatibility class II compartment, and elicits enhanced immune responses. J Biol Chem 278(39):37926–37936

    Article  PubMed  CAS  Google Scholar 

  • Massaer M, Mazzu P, Haumont M, Magi M, Daminet V, Bollen A, Jacquet A (2001) High-level expression in mammalian cells of recombinant house dust mite allergen ProDer p 1 with optimized codon usage. Int Arch Allergy Immunol 125(1):32–43

    Article  PubMed  CAS  Google Scholar 

  • Morris-Downes MM, Phenix KV, Smyth J, Sheahan BJ, Lileqvist S, Mooney DA, Liljestrom P, Todd D, Atkins GJ (2001) Semliki forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems. Vaccine 19(15–16):1978–1988

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee P, Dani A, Bhatia S, Singh N, Rudensky AY, George A, Bal V, Mayor S, Rath S (2001) Efficient presentation of both cytosolic and endogenous transmembrane protein antigens on MHC class II is dependent on cytoplasmic proteolysis. J Immunol 167(5):2632–2641

    PubMed  CAS  Google Scholar 

  • Pascolo S (2008) Vaccination with messenger RNA (mRNA). Handb Exp Pharmacol 183:221–235

    Article  PubMed  CAS  Google Scholar 

  • Peters M, Kauth M, Scherner O, Gehlhar K, Steffen I, Wentker P, von Mutius E, Holst O, Bufe A (2010) Arabinogalactan isolated from cowshed dust extract protects mice from allergic airway inflammation and sensitization. J Allergy Clin Immunol 126(3):648–656, e641-644

    Article  PubMed  CAS  Google Scholar 

  • Pfefferle PI, Sel S, Ege MJ, Buchele G, Blumer N, Krauss-Etschmann S, Herzum I, Albers CE, Lauener RP, Roponen M, Hirvonen MR, Vuitton DA, Riedler J, Brunekreef B, Dalphin JC, Braun-Fahrlander C, Pekkanen J, von Mutius E, Renz H (2008) Cord blood allergen-specific IgE is associated with reduced IFN-gamma production by cord blood cells: the protection against allergy-study in rural environments (PASTURE) study. J Allergy Clin Immunol 122(4):711–716

    Article  PubMed  CAS  Google Scholar 

  • Purohit A, Niederberger V, Kronqvist M, Horak F, Gronneberg R, Suck R, Weber B, Fiebig H, van Hage M, Pauli G, Valenta R, Cromwell O (2008) Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives. Clin Exp Allergy 38(9):1514–1525

    Article  PubMed  CAS  Google Scholar 

  • 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(10):5141–5145

    Article  PubMed  CAS  Google Scholar 

  • Riedler J, Eder W, Oberfeld G, Schreuer M (2000) Austrian children living on a farm have less hay fever, asthma and allergic sensitization. Clin Exp Allergy 30(2):194–200

    Article  PubMed  CAS  Google Scholar 

  • Riedler J, Braun-Fahrlander C, Eder W, Schreuer M, Waser M, Maisch S, Carr D, Schierl R, Nowak D, von Mutius E (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358(9288):1129–1133

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez F, Harkins S, Redwine JM, de Pereda JM, Whitton JL (2001) CD4(+) T cells induced by a DNA vaccine: immunological consequences of epitope-specific lysosomal targeting. J Virol 75(21):10421–10430

    Article  PubMed  CAS  Google Scholar 

  • Roesler E, Weiss R, Weinberger EE, Fruehwirth A, Stoecklinger A, Mostbock S, Ferreira F, Thalhamer J, Scheiblhofer S (2009) Immunize and disappear-safety-optimized mRNA vaccination with a panel of 29 allergens. J Allergy Clin Immunol 124(5):1070–1077, e1071-1011

    Article  PubMed  CAS  Google Scholar 

  • Romagnani S (2004) The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both? Immunology 112(3):352–363

    Article  PubMed  CAS  Google Scholar 

  • Scheiblhofer S, Gabler M, Leitner WW, Bauer R, Zoegg T, Ferreira F, Thalhamer J, Weiss R (2006) Inhibition of type I allergic responses with nanogram doses of replicon-based DNA vaccines. Allergy 61(7):828–835

    Article  PubMed  CAS  Google Scholar 

  • Scheiblhofer S, Stoecklinger A, Gruber C, Hauser-Kronberger C, Alinger B, Hammerl P, Thalhamer J, Weiss R (2007) Gene gun immunization with clinically relevant allergens aggravates allergen induced pathology and is contraindicated for allergen immunotherapy. Mol Immunol 44(8):1879–1887

    Article  PubMed  CAS  Google Scholar 

  • Senthilselvan A, Rennie D, Chenard L, Burch LH, Babiuk L, Schwartz DA, Dosman JA (2008) Association of polymorphisms of toll-like receptor 4 with a reduced prevalence of hay fever and atopy. Ann Allergy Asthma Immunol 100(5):463–468

    Article  PubMed  Google Scholar 

  • Sudre B, Vacheyrou M, Braun-Fahrlander C, Normand AC, Waser M, Reboux G, Ruffaldi P, von Mutius E, Piarroux R (2009) High levels of grass pollen inside European dairy farms: a role for the allergy-protective effects of environment? Allergy 64(7):1068–1073

    Article  PubMed  CAS  Google Scholar 

  • Tavernier G, Andries O, Demeester J, Sanders NN, De Smedt SC, Rejman J (2010) mRNA as gene therapeutic: How to control protein expression. J Control Release 150(3):238–247

    Article  PubMed  Google Scholar 

  • Thalhamer J, Weiss R, Roesler E, Scheiblhofer S, Fruehwirth A (2009) RNA vaccines. WO/2009/040443

    Google Scholar 

  • Thalhamer T, Dobias H, Stepanoska T, Proll M, Stutz H, Dissertori O, Lackner P, Ferreira F, Wallner M, Thalhamer J, Hartl A (2010) Designing hypoallergenic derivatives for allergy treatment by means of in silico mutation and screening. J Allergy Clin Immunol 125(4):926–934, e910

    Article  PubMed  CAS  Google Scholar 

  • Valenta R, Ferreira F, Focke-Tejkl M, Linhart B, Niederberger V, Swoboda I, Vrtala S (2010) From allergen genes to allergy vaccines. Annu Rev Immunol 28:211–241

    Article  PubMed  CAS  Google Scholar 

  • Van Overtvelt L, Wambre E, Maillere B, von Hofe E, Louise A, Balazuc AM, Bohle B, Ebo D, Leboulaire C, Garcia G, Moingeon P (2008) Assessment of Bet v 1-specific CD4+ T cell responses in allergic and nonallergic individuals using MHC class II peptide tetramers. J Immunol 180(7):4514–4522

    PubMed  Google Scholar 

  • Van Ree R, Van Leeuwen WA, Dieges PH, Van Wijk RG, De Jong N, Brewczyski PZ, Kroon AM, Schilte PP, Tan KY, Simon-Licht IF, Roberts AM, Stapel SO, Aalberse RC (1997) Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy. Clin Exp Allergy 27(1):68–74

    Article  PubMed  Google Scholar 

  • van Strien RT, Engel R, Holst O, Bufe A, Eder W, Waser M, Braun-Fahrlander C, Riedler J, Nowak D, von Mutius E (2004) Microbial exposure of rural school children, as assessed by levels of N-acetyl-muramic acid in mattress dust, and its association with respiratory health. J Allergy Clin Immunol 113(5):860–867

    Article  PubMed  Google Scholar 

  • Vogel K, Blumer N, Korthals M, Mittelstadt J, Garn H, Ege M, von Mutius E, Gatermann S, Bufe A, Goldmann T, Schwaiger K, Renz H, Brandau S, Bauer J, Heine H, Holst O (2008) Animal shed Bacillus licheniformis spores possess allergy-protective as well as inflammatory properties. J Allergy Clin Immunol 122(2):307–312, 312 e301–308

    Article  PubMed  Google Scholar 

  • Von Ehrenstein OS, Von Mutius E, Illi S, Baumann L, Bohm O, von Kries R (2000) Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy 30(2):187–193

    Article  Google Scholar 

  • von Mutius E, Vercelli D (2010) Farm living: effects on childhood asthma and allergy. Nat Rev Immunol 10(12):861–868

    Article  Google Scholar 

  • Weiss R, Scheiblhofer S, Freund J, Ferreira F, Livey I, Thalhamer J (2002) Gene gun bombardment with gold particles displays a particular Th2-promoting signal that over-rules the Th1-inducing effect of immunostimulatory CpG motifs in DNA vaccines. Vaccine 20(25–26):3148–3154

    Article  PubMed  CAS  Google Scholar 

  • Weiss R, Scheiblhofer S, Gabler M, Ferreira F, Leitner WW, Thalhamer J (2006) Is genetic vaccination against allergy possible? Int Arch Allergy Immunol 139(4):332–345

    Article  PubMed  CAS  Google Scholar 

  • Weiss R, Scheiblhofer S, Roesler E, Ferreira F, Thalhamer J (2010) Prophylactic mRNA vaccination against allergy. Curr Opin Allergy Clin Immunol 10(6):567–574

    Article  PubMed  CAS  Google Scholar 

  • Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247(4949 Pt 1):1465–1468

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowlegement

This work was supported by Biomay AG, Vienna, Austria and the Christian Doppler Research Association, Vienna, Austria.

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Division of Allergy and Immunology, University of Salzburg, Salzburg, Austria

    Richard Weiss, Sandra Scheiblhofer, Elisabeth Rösler & Josef Thalhamer

Authors
  1. Richard Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandra Scheiblhofer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elisabeth Rösler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Josef Thalhamer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Josef Thalhamer .

Editor information

Editors and Affiliations

  1. , Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Josef Thalhamer

  2. , Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Richard Weiss

  3. , Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Sandra Scheiblhofer

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag/Wien

About this chapter

Cite this chapter

Weiss, R., Scheiblhofer, S., Rösler, E., Thalhamer, J. (2012). DNA and RNA Vaccines for Prophylactic and Therapeutic Treatment of Type I Allergy. In: Thalhamer, J., Weiss, R., Scheiblhofer, S. (eds) Gene Vaccines. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0439-2_12

Download citation

Publish with us

Policies and ethics

Search

Navigation