Vaccines against Allergies (Current Topics in Microbiology and Immunology Book 352)

The pathomechanisms of allergy are quite well investigated and the disease-causing allergens are characterized in great detail down to their molecular structures. We are thus beginning to see several new strategies for allergen-specific immunotherapy on the horizon, several of which are summarized in this issue. It thus seems that hundred years after the first experimental attempts to "(Bdesensitize" hayfever patients we are now capable of developing powerful and rational forms of immunotherapy which hold promise for curing allergy sufferers and eventually may allow real prophylactic vaccination against allergy. It is thus quite possible that allergy may become eradicated similar as certain forms of infectious diseases through vaccination Cover 1 Current Topics in Microbiology and Immunology 352 2 Vaccines against Allergies 4 ISBN 9783642200533 5 Preface 6 Contents 8 Contributors 10 Immunological Approaches for Tolerance Induction in Allergy 14 Abstract 14 1...Introduction 15 2...The Immune Response to Allergens is Regulated by T cells 16 3...Tolerance 18 4...Current Treatments for Allergy 20 5...Tolerance Induction 20 5.1 The T Cell Response and Cytokine Secretion 21 5.2 Histamine and Histamine Receptors in Tolerance Induction 23 5.3 B Cells in Tolerance Induction 23 5.4 Innate Immunity and Tolerance Induction 24 6...Improving Current Immunotherapy Strategies 25 6.1 Allergen: Immunogenicity and Allergenicity 25 6.2 Type of Allergen 26 6.2.1 Native Allergens 26 6.2.2 ‘Allergoid’xe ‘‘Allergoids’: Chemically Modified Allergens 27 6.2.3 Recombinant Allergens 27 6.3 Modality: Route of Dosing 29 6.4 Adjuvant 30 7...Future Perspectives 31 8...Conclusion 31 References 32 Clinical Experience with Recombinant Molecules for Allergy Vaccination 40 Abstract 40 1...Considerations for Optimal Allergen Specific Immunotherapy 41 2...Allergen Variants with Reduced IgE-Binding Activity 43 3...Recombinant Grass and Birch Pollen Allergens 44 4...Recombinant Hypoallergenic Variants of Birch Pollen Allergen Bet v 1 46 5...Recombinant Cat Allergen Fel d 1 50 6...Ragweed Amb a 1 51 7...Where Do We Go from Here? 52 References 52 Allergen-Specific Immunotherapy with Recombinant Allergens 56 Abstract 56 1...Introduction 57 2...Strategies for Improving Efficacy of Allergen-Specific Immunotherapy 57 3...Clinical Trials 58 4...Clinical Efficacy and Side Effects of Recombinant Allergens 59 4.1 Recombinant Grass Allergen Immunotherapy 59 4.2 Recombinant Birch Allergen Immunotherapy 60 4.3 Recombinant Birch Allergen Derivatives Immunotherapy 61 5...Discussion 62 5.1 Clinical Efficacy and Safety of Recombinant Allergens 63 5.2 Clinical Efficacy and Safety of Recombinant Hypoallergenic Derivatives 64 5.3 Future Perspectives 65 6...Conclusions 65 References 65 Vaccine Approaches for Food Allergy 68 Abstract 68 1...Background 69 2...Immune Responses to Food Antigens and Mechanisms of Oral Tolerance 70 3...Therapeutic Approaches 72 3.1 Allergen-Specific Strategies 73 3.1.1 Subcutaneous Immunotherapy 73 3.1.2 Sublingual and Oral Immunotherapy 75 3.1.3 Immunotherapy with Engineered Food Proteins 77 3.1.4 Peptide Immunotherapy 77 3.1.5 Plasmid DNA Immunotherapy 77 3.1.6 Immunotherapy with Immune Stimulatory Sequences 78 3.1.7 Diet-Specific Tolerance Promotion 78 3.2 Allergen Non-Specific Strategies 78 3.2.1 Anti-IgE Therapy 78 3.2.2 Chinese Herbal Medicine 79 3.2.3 Cytokine Therapies 79 4...Conclusions 79 References 80 Intralymphatic Immunotherapy: From the Rationale to Human Applications 84 Abstract 84 1...Introduction 85 1.1 The Function of Lymph Nodes 85 1.2 Targeting Antigen to Lymph Nodes 86 1.3 Intralymphatic Immunotherapy (ILIT) with Dendritic Cells 87 1.4 ILIT with Tumor Cells 87 1.5 ILIT with MHC Class I Binding Peptides 88 1.6 ILIT with Naked DNA 88 1.7 ILIT with RNA-Based Vaccines 88 1.8 Intralymphatic Vaccination with Vaccinia Virus 88 1.9 ILIT with ISCOMS 89 1.10 ILIT with Protein-Based Vaccines 89 1.11 ILIT with BCG 89 1.12 ILIT with Adjuvants 90 1.13 Inefficient Vaccines Profit the Most from Intralymphatic Administration 90 1.14 ILIT with Allergens 90 1.15 Biodistribution After Intralymphatic Versus Subcutaneous Injection in Humans 92 1.16 Clinical Trials on ILIT with Bee Venom 93 1.17 Clinical Trials on ILIT to Treat Pollen-Induced Hay Fever 93 1.18 Future Direction 93 1.19 Is ILIT Difficult or Painful? 94 References 94 Induction of Allergen-Specific Tolerance via Mucosal Routes 98 Abstract 98 1...Introduction 99 2...Tolerance Induction by Mucosal Immunotherapy 100 2.1 General Comments 100 2.2 Intranasal Immunotherapy 101 2.3 Oral Immunotherapy 106 2.4 Sublingual Immunotherapy 108 3...Interest in Adjuvants and Vector Systems for Mucosal Immunization 109 4...Conclusions 110 References 111 T Cell Epitope-Based Allergy Vaccines 120 Abstract 120 1...Introduction 121 2...Clinical Studies 123 3...Insect Venom Allergy 126 4...Mechanisms of Peptide-Induced Tolerance 127 5...Future Peptide Vaccine Design 128 6...Summary 129 Acknowledgments 129 References 129 Allergen-Specific Immunotherapy: Towards Combination Vaccines for Allergic and Infectious Diseases 134 Abstract 134 1...Introduction 135 2...Developments in the Field of Allergen-specific Immunotherapy 136 3...The Impact of Recombinant Allergens on SIT 138 3.1 Recombinant Wildtype Allergens 139 3.2 Hypoallergenic Allergen Derivatives 140 3.3 Recombinant Hybrid Molecules 140 3.4 DNA Vaccines 140 3.5 Allergen Conjugates 141 3.6 T Cell Epitope Peptides 141 3.7 Allergen-Derived Peptides Lacking Allergenic Activity to Induce Allergen-Specific Blocking IgG Antibodies 142 4...Combination Vaccine against Allergies and Infectious Diseases 143 References 148 Passive Immunization with Allergen-Specific Antibodies 154 Abstract 154 1...Background 155 2...Beneficial Role of Allergen-Specific Blocking IgG Antibodies 156 3...Isolation and Characterization of Allergen-Specific IgG Antibodies for Therapy and Prevention 159 3.1 Epitope Specificity and Titer 160 3.2 Cross-Reactivity 161 3.3 Affinity 161 3.4 Half-Life and Clearance 162 3.5 Binding to Fc Receptors 164 3.6 Safety of Recombinant Monoclonal Antibodies 165 4...Proof of Concept Testing in Animal Models 165 5...Possible Application of Allergen-Specific IgG for Therapy and Prophylaxis 166 References 167 Cell-Based Therapy in Allergy 174 Abstract 174 1...Introduction 175 2...Prevention of Allergy by Induction of Peripheral Tolerance 175 2.1 Induction of Tolerance via the Mucosal Route 176 2.2 Induction of Tolerance by Intradermal Peptide Application 176 2.3 Tregs as Cell-Based Therapy in Allergy 177 3...Tolerance Induction by Hematopoietic Stem Cell Transplantation (HSCT) 178 3.1 Mixed Chimerism 179 3.2 Molecular Chimerism 180 3.2.1 Introduction of Allo- and Xeno- Genes to Establish Tolerance 180 3.2.2 Introduction of Auto-Antigens to Establish Tolerance 181 3.3 Hematopoietic Stem Cell Transplantation and Allergy 182 4...Induction of Tolerance via Molecular Chimerism in Allergy 182 4.1 Prevention of Allergy by Induction of Tolerance via Molecular Chimerism 182 4.2 Anticipated Impediments to Translate Molecular Chimerism to the Clinical Setting and Possible Solutions 183 4.2.1 Moving to Safer Protocols 183 4.2.2 Avoiding Anaphylaxis 185 5...Conclusion 185 References 185 Index 194 3642200532,9783642200533 Springer 2011 We are celebrating this year the hundred years ́ anniversary of allergen-specific immunotherapy. In 1911 Leonard Noon published his seminal work “Prophylactic inoculation against hay fever” describing his attempts to achieve active immunity against “grass pollen toxin” by administering increasing doses of grass pollen extract before the grass pollen season to allergic patients. Although it was unknown at that time that allergy represents an immunological hypersensitivity disease, the treatment was effective and many observations made by Noon remained valid until today. Today allergen-specific immunotherapy is well established as the only allergen-specific and disease-modifying treatment for IgE-mediated allergies and has long-lasting effects. In fact, more than 25% of the population suffer from IgE-mediated allergies which therefore represent a major health burden of our society, particularly because untreated allergy often progresses to severe disabling forms of disease, such as asthma and sometimes kills sensitized people through anaphylaxis. Immunological approaches for tolerance induction in allergy / Melanie L. Conrad, Harald Renz and Kurt Blaser Clinical experience with recombinant molecules for allergy vaccination / Oliver Cromwell ... [et al.] Allergen-specific immunotherapy with recombinant allergens / G. Pauli and Hans-Jorgen Malling Vaccine approaches for food allergy / Philip Rancitelli, Alison Hofmann and A. Wesley Burks Intralymphatic immunotherapy : from the rationale to human applications / Gabriela Senti, Pal Johansen and Thomas M. Kundig Induction of allergen-specific tolerance via mucosal routes / Laurent Mascarell ... [et al.] T cell epitope-based allergy vaccines / Mark Larche Allergen-specific immunotherapy : towards combination vaccines for allergic and infectious diseases / Johanna Edlmayr ... [et al.] Passive immunization with allergen-specific antibodies / Sabine Flicker ... [et al.] Cell-based therapy in allergy / Ulrike Baranyi ... [et al.]. Front Matter....Pages i-xi Immunological Approaches for Tolerance Induction in Allergy....Pages 1-26 Clinical Experience with Recombinant Molecules for Allergy Vaccination....Pages 27-42 Allergen-Specific Immunotherapy with Recombinant Allergens....Pages 43-54 Vaccine Approaches for Food Allergy....Pages 55-69 Intralymphatic Immunotherapy: From the Rationale to Human Applications....Pages 71-84 Induction of Allergen-Specific Tolerance via Mucosal Routes....Pages 85-105 T Cell Epitope-Based Allergy Vaccines....Pages 107-119 Allergen-Specific Immunotherapy: Towards Combination Vaccines for Allergic and Infectious Diseases....Pages 121-140 Passive Immunization with Allergen-Specific Antibodies....Pages 141-159 Cell-Based Therapy in Allergy....Pages 161-179 Back Matter....Pages 181-182