Novel vaccines and adjuvants for allergen-specific immunotherapy.

Advances in genetic engineering and biotechnology, in parallel to increased understanding of disease processes and mechanisms of protective immunity, have facilitated the development of novel rational vaccination concepts for allergy. The spectrum ranges from utilizing recombinant proteins, peptides, new adjuvants, immunomodulatory therapy and DNA vaccines, to use of new application routes for both prophylaxis and treatment of allergic disease. New therapeutic concepts based on patient-tailored immunotherapy using recombinant allergens, anti-IgE and sublingual immunotherapies are slowly moving from the bench to the clinics. The additive value of new treatments above existing therapies must be, however, focused on the improvement of efficacy for long-term cure and increased patient compliance to warrant a broad applicability that has to compete with the symptomatic control of allergic and asthmatic diseases of currently available drugs.

[1]  T. Kündig,et al.  Efficacy and Safety of Allergen-Specific Immunotherapy in Rhinitis, Rhinoconjunctivitis, and Bee/Wasp Venom Allergies , 2005, International reviews of immunology.

[2]  G. D'Amato Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory diseases. , 2006, European journal of pharmacology.

[3]  A. Kay,et al.  Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial , 2002, The Lancet.

[4]  J. Damoiseaux Regulatory T cells: back to the future. , 2006, The Netherlands journal of medicine.

[5]  C. Akdis,et al.  Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells , 2004, The Journal of experimental medicine.

[6]  C. Akdis,et al.  Prevention of allergy by a recombinant multi‐allergen vaccine with reduced IgE binding and preserved T cell epitopes , 2005, European journal of immunology.

[7]  T. Bieber Allergen‐specific sublingual immunotherapy: less mystic, more scientific , 2006, Allergy.

[8]  N. Restifo,et al.  The promise of nucleic acid vaccines , 2000, Gene Therapy.

[9]  F. Simons,et al.  Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA. , 2004, The Journal of allergy and clinical immunology.

[10]  Tomoko Hayashi,et al.  Airway peptidoglycan and immunostimulatory DNA exposures have divergent effects on the development of airway allergen hypersensitivities. , 2004, The Journal of allergy and clinical immunology.

[11]  W. Leitner,et al.  Is Genetic Vaccination against Allergy Possible? , 2006, International Archives of Allergy and Immunology.

[12]  Hans Hengartner,et al.  Antigen localisation regulates immune responses in a dose‐ and time‐dependent fashion: a geographical view of immune reactivity , 1997, Immunological reviews.

[13]  C. Akdis,et al.  A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy. , 2005, The Journal of allergy and clinical immunology.

[14]  Scott A. Smith,et al.  Aluminum sulfate significantly reduces the skin test response to common allergens in sensitized patients , 2006, Clinical and molecular allergy : CMA.

[15]  R. Zinkernagel,et al.  Intralymphatic immunization enhances DNA vaccination , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. Hawrylowicz Regulatory T cells and IL-10 in allergic inflammation , 2005, The Journal of experimental medicine.

[17]  Giorgio Walter Canonica,et al.  Allergen immunotherapy: therapeutic vaccines for allergic diseases , 1998 .

[18]  L. O’Neill,et al.  How Toll-like receptors signal: what we know and what we don't know. , 2006, Current opinion in immunology.

[19]  H. Grönlund,et al.  Vaccination with genetically engineered allergens prevents progression of allergic disease , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Heimo Breiteneder,et al.  Pollen allergens are restricted to few protein families and show distinct patterns of species distribution. , 2006, The Journal of allergy and clinical immunology.

[21]  S. Akira Mammalian Toll-like receptors. , 2003, Current opinion in immunology.

[22]  R. von Baehr,et al.  Allergoid-specific T-cell reaction as a measure of the immunological response to specific immunotherapy (SIT) with a Th1-adjuvanted allergy vaccine. , 2005, Journal of investigational allergology & clinical immunology.

[23]  B. Wüthrich,et al.  Direct intralymphatic injection of peptide vaccines enhances immunogenicity , 2005, European journal of immunology.

[24]  R. Crameri Correlating IgE reactivity with three-dimensional structure. , 2003, The Biochemical journal.

[25]  Cezmi A Akdis,et al.  T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. , 2005, The Journal of allergy and clinical immunology.

[26]  S. Durham,et al.  Grass Pollen Immunotherapy Induces Mucosal and Peripheral IL-10 Responses and Blocking IgG Activity1 , 2004, The Journal of Immunology.

[27]  P. Potter Update on sublingual immunotherapy. , 2006, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[28]  K. Hoffmann‐Sommergruber,et al.  Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v 1: potential use of hypoallergenic isoforms for immunotherapy , 1996, The Journal of experimental medicine.

[29]  D. Graft Insect sting allergy. , 2006, The Medical clinics of North America.

[30]  L. Heinzerling,et al.  Critical role for DNA vaccination frequency in induction of antigen-specific cytotoxic responses. , 2006, Vaccine.

[31]  M. Larché,et al.  The effect of Fel d 1‐derived T‐cell peptides on upper and lower airway outcome measurements in cat‐allergic subjects , 2005, Allergy.

[32]  M. Gajhede,et al.  Allergy Vaccine Engineering: Epitope Modulation of Recombinant Bet v 1 Reduces IgE Binding but Retains Protein Folding Pattern for Induction of Protective Blocking-Antibody Responses1 , 2004, The Journal of Immunology.

[33]  A. Kay,et al.  T Cell Epitope Immunotherapy Induces a CD4+ T Cell Population with Regulatory Activity , 2005, PLoS medicine.

[34]  A. Woodcock,et al.  Fungal contamination of bedding , 2006, Allergy.

[35]  C. Akdis,et al.  Mechanisms of immune suppression by interleukin‐10 and transforming growth factor‐β: the role of T regulatory cells , 2006, Immunology.

[36]  J Bousquet,et al.  Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. , 1998, The Journal of allergy and clinical immunology.

[37]  Michael B. Stadler,et al.  Allergenicity prediction by protein sequence , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[38]  L. Vailes,et al.  Quantitation of the major fungal allergens, Alt a 1 and Asp f 1, in commercial allergenic products. , 2001, The Journal of allergy and clinical immunology.

[39]  M. Worm,et al.  Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi‐centre, randomized, dose–response study , 2006, Allergy.

[40]  Y. Deniz,et al.  Safety and tolerability of omalizumab (Xolair®), a recombinant humanized monoclonal anti-IgE antibody , 2005, Clinical reviews in allergy & immunology.

[41]  R. Valenta,et al.  A hybrid molecule resembling the epitope spectrum of grass pollen for allergy vaccination. , 2005, The Journal of allergy and clinical immunology.

[42]  C. Akdis,et al.  Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. , 1998, The Journal of allergy and clinical immunology.

[43]  M. Lahoz,et al.  Evaluation of Omalizumab From a Health Plan Perspective , 2005, Journal of managed care pharmacy : JMCP.

[44]  Rudolf Valenta,et al.  Molecular design of allergy vaccines. , 2005, Current opinion in immunology.

[45]  T. Kündig,et al.  Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults. , 2006, The Journal of allergy and clinical immunology.

[46]  Sergio Romagnani,et al.  Immunologic influences on allergy and the TH1/TH2 balance. , 2004, The Journal of allergy and clinical immunology.

[47]  T. Thalhamer,et al.  Generation of hypoallergenic DNA vaccines by forced ubiquitination: preventive and therapeutic effects in a mouse model of allergy. , 2006, The Journal of allergy and clinical immunology.

[48]  M. Belvisi,et al.  New anti-inflammatory therapies and targets for asthma and chronic obstructive pulmonary disease , 2004, Expert opinion on therapeutic targets.

[49]  C. Akdis,et al.  Cytokine and Antibody Responses in Birch-Pollen-Allergic Patients Treated with Genetically Modified Derivatives of the Major Birch Pollen Allergen Bet v 1 , 2005, International Archives of Allergy and Immunology.

[50]  C. Akdis,et al.  Immunological mechanisms of sublingual immunotherapy , 2006, Allergy.

[51]  B. Wüthrich,et al.  Toll‐like receptor ligands as adjuvants in allergen‐specific immunotherapy , 2005, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[52]  M. Jutel,et al.  Allergen-specific immunotherapy with recombinant grass pollen allergens. , 2005, The Journal of allergy and clinical immunology.

[53]  Franz König,et al.  Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. , 2005, The Journal of allergy and clinical immunology.

[54]  A. B. Kay,et al.  The role of T lymphocytes in asthma. , 2006, Chemical immunology and allergy.

[55]  Nacksung Kim,et al.  Protective effect of the DNA vaccine encoding the major house dust mite allergens on allergic inflammation in the murine model of house dust mite allergy , 2006, Clinical and molecular allergy : CMA.

[56]  P. Neudecker,et al.  Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure. , 2003, The Biochemical journal.

[57]  W. Pichler,et al.  Reduced in vivo allergenicity of Bet v 1d isoform, a natural component of birch pollen. , 1999, The Journal of allergy and clinical immunology.

[58]  M. Dallman,et al.  Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease , 2004, The Lancet.

[59]  R. Crameri,et al.  Regulation of the IgE response at the molecular level: impact on the development of systemic anti IgE therapeutic strategies. , 2006, Chemical immunology and allergy.

[60]  M. Larché,et al.  Peptide-based immunotherapy: a novel strategy for allergic disease , 2005, Expert review of vaccines.

[61]  C. Akdis,et al.  Absence of T-regulatory cell expression and function in atopic dermatitis skin. , 2006, The Journal of allergy and clinical immunology.

[62]  H. Malling,et al.  Side‐effects of allergen‐specific immunotherapy. A prospective multi‐centre study , 2006, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[63]  S. Vieths,et al.  Allergy vaccines: a need for standardisation in mass units of major allergen. , 2005, Pharmeuropa bio.

[64]  R. Schreiber,et al.  Definition of target antigens for naturally occurring CD4+ CD25+ regulatory T cells , 2005, The Journal of experimental medicine.

[65]  M. Gershwin,et al.  Why Do People Die of Anaphylaxis?—A Clinical Review , 2005, Clinical & developmental immunology.

[66]  R. Coffman,et al.  Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction , 2005, The Journal of experimental medicine.