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Background: Treatment of patients with cat allergy with peptides derived from Fel d 1 (the major cat allergen) ameliorated symptoms of cat allergy in phase 2 clinical trials., Objective: We sought to demonstrate that the tolerance induced by Fel d 1 peptide immunotherapy can be exploited to reduce allergic responses to a second allergen, ovalbumin (OVA), in mice sensitized dually to OVA and Fel d 1., Methods: Induction of tolerance to OVA was achieved through simultaneous exposure to both allergens after peptide treatment. Functional tolerance to each allergen was assessed in a model of allergic airways disease in which treated mice were protected from eosinophilia, goblet cell hyperplasia, and T H 2 cell infiltration., Results: Suppression of allergic responses to cat allergen challenge was associated with significant increases in numbers of CD4 + CD25 + Foxp3 + T cells, IL-10 + cells, and CD19 + IL-10 + B cells, whereas the response to OVA was associated with a marked reduction in numbers of T H 2 cytokine-secreting T cells and less prominent changes in outcomes associated with immune regulation., Conclusions: These observations suggest that immune tolerance induced by peptide immunotherapy can be used experimentally to treat an allergic response to another allergen and that the molecular mechanisms underlying induction of tolerance to a treatment-specific allergen and a bystander allergen might be different., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Synthetic peptide immunoregulatory epitopes are a new class of immunotherapy to treat allergic rhinoconjunctivitis (ARC). Grass allergen peptides, comprising 7 synthetic T-cell epitopes derived from Cyn d 1, Lol p 5, Dac g 5, Hol l 5, and Phl p 5, is investigated for treatment of grass pollen-induced ARC., Objective: We sought to evaluate the efficacy, safety, and tolerability of intradermally administered grass allergen peptides., Methods: A multicenter, randomized, double-blind, placebo-controlled study evaluated 3 regimens of grass allergen peptides versus placebo in patients with grass pollen-induced allergy (18-65 years). After a 4-day baseline challenge to rye grass in the environmental exposure unit (EEU), subjects were randomized to receive grass allergen peptides at 6 nmol at 2-week intervals for a total of 8 doses (8x6Q2W), grass allergen peptides at 12 nmol at 4-week intervals for a total of 4 doses (4x12Q4W), or grass allergen peptides at 12 nmol at 2-week intervals for a total of 8 doses (8x12Q2W) or placebo and treated before the grass pollen season. The primary efficacy end point was change from baseline in total rhinoconjunctivitis symptom score across days 2 to 4 of a 4-day posttreatment challenge (PTC) in the EEU after the grass pollen season. Secondary efficacy end points and safety were also assessed., Results: Two hundred eighty-two subjects were randomized. Significantly greater improvement (reduction of total rhinoconjunctivitis symptom score from baseline to PTC) occurred across days 2 to 4 with grass allergen peptide 8x6Q2W versus placebo (-5.4 vs -3.8, respectively; P = .0346). Greater improvement at PTC also occurred for grass allergen peptide 8x6Q2W versus placebo (P = .0403) in patients with more symptomatic ARC. No safety signals were detected., Conclusion: Grass allergen peptide 8x6Q2W significantly improved ARC symptoms after rye grass allergen challenge in an EEU with an acceptable safety profile., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In this review, we report on relevant current topics in allergen immunotherapy (AIT) which were broadly discussed during the first Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December 2015 by leading clinicians, scientists and industry representatives in the field. The aim of this symposium was to highlight AIT-related aspects of public health, clinical efficacy evaluation, mechanisms, development of new biomarkers and an overview of novel therapeutic approaches. Allergy is a public health issue of high socioeconomic relevance, and development of evidence-based action plans to address allergy as a public health issue ought to be on national and regional agendas. The underlying mechanisms are in the focus of current research that lays the ground for innovative therapies. Standardization and harmonization of clinical endpoints in AIT trials as well as current knowledge about potential biomarkers have substantiated proof of effectiveness of this disease-modifying therapeutic option. Novel treatments such as peptide immunotherapy, intralymphatic immunotherapy and use of recombinant allergens herald a new age in which AIT may address treatment of allergy as a public health issue by reaching a large fraction of patients., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities., Methods: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation., Results: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues., Conclusion: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cat-PAD, the first in a new class of synthetic peptide immuno-regulatory epitopes (SPIREs), was shown to significantly improve rhinoconjunctivitis symptoms in subjects with cat allergy up to 1 year after the start of a short course of treatment., Objective: To evaluate the long-term effects of Cat-PAD on rhinoconjunctivitis symptoms following standardized allergen challenge 2 years after treatment., Methods: In a randomized, double-blind, placebo-controlled, parallel group study, subjects were exposed to cat allergen in an environmental exposure chamber (EEC) before and after treatment with two regimens of Cat-PAD (either eight doses of 3 nmol or four doses of 6 nmol) given intradermally over a 3-month period. In this follow-up study, changes from baseline in rhinoconjunctivitis symptoms were reassessed 2 years after the start of treatment., Results: The primary endpoint showed a mean reduction in total rhinoconjunctivitis symptom scores of 3.85 units in the 4 × 6 nmol Cat-PAD group compared to placebo 2 years after the start of treatment (P = 0.13), and this difference was statistically significant in the secondary endpoint at the end of day 4 when the cumulative allergen challenge was greatest (P = 0.02). Consistent reductions in nasal symptoms of between 2 and 3 units were observed for 4 × 6 nmol Cat-PAD compared to placebo between the 2 and 3 h time points on days 1-4 of EEC challenge at 2 years (P < 0.05). The 8 × 3 nmol dose did not show a meaningful effect in this study., Conclusion and Clinical Relevance: A persistent, clinically meaningful reduction in rhinoconjunctivitis symptoms was observed on EEC challenge 2 years after the start of a short course of treatment with 4 × 6 nmol Cat-PAD. This study is the first to provide evidence of a long-term therapeutic effect with this new class of SPIREs., (© 2015 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.)

Allergen immunotherapy with whole proteins is clinically efficacious but requires a protracted treatment period because of frequent allergic adverse events. A combination of duration of treatment and adverse events leads to poor compliance. Short synthetic peptides containing the major immunodominant T cell epitopes of allergenic proteins have been shown to reduce IgE cross-linking ability, thereby leading to fewer allergic adverse events following their administration to patients with allergies. Peptide immunotherapy has been shown to result in clinically meaningful efficacy in several Phase II, randomized, double-blind, placebo-controlled clinical trials. Exactly how peptide immunotherapy achieves its efficacy remains incompletely understood, but the mechanisms are thought to include immune deviation and induction of regulatory T cells capable of suppressing allergen-specific immune responses. Limited data are available on the effects of peptide therapy on humoral immune responses. Induction of allergen-specific IgG has been observed after peptide therapy, but the levels of antibody induced were much lower than generally seen with the utilization of whole allergen approaches. Thus, the immunological mechanisms of peptide immunotherapy appear to overlap, although not completely, with those seen in whole allergen therapy. Further studies are required to fully elucidate mechanisms of action.

Background: Allergic rhinoconjunctivitis is an increasingly common source of morbidity, with sensitivity to cats accounting for 10% to 15% of disease burden. Allergy to cats is also a major risk factor for the development of asthma., Objectives: We sought to probe the persistence of the treatment effect of a novel F el d 1-derived peptide antigen desensitization (Cat-PAD) 1 year after the start of treatment in subjects with cat allergy-induced rhinoconjunctivitis after standardized allergen challenge., Methods: In a randomized, double-blind, placebo-controlled, parallel-group clinical trial, subjects attended an environmental exposure chamber in which they were exposed to cat allergen before and after treatment with 2 different regimens of Cat-PAD over a 3-month period. Clinical efficacy was assessed as a change in total rhinoconjunctivitis symptom scores 18 to 22 weeks and 50 to 54 weeks after the start of treatment., Results: Treatment with Cat-PAD showed greater efficacy with 4 administrations of a 6-nmol dose 4 weeks apart than with 8 administrations of a 3-nmol dose 2 weeks apart. The treatment effect of 6 nmol persisted 1 year after the start of treatment and was significantly different from that of 3 nmol (P = .0342) and placebo (P = .0104). The treatment effect was apparent on both nasal and ocular symptoms at 1 year., Conclusions: A short course of Cat-PAD improves the ocular and nasal components of rhinoconjunctivitis symptoms in subjects with cat allergy, with the treatment effect persisting 1 year after the start of treatment., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Induction of allergen-specific IgG(4) antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG(4) antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen-specific IgG(4) titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG-associated inhibitory activity such as inhibition of IgE-allergen interactions (IgE-blocking factor) and inhibition of CD23-dependent IgE-facilitated allergen binding (IgE-FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response., Methods: In an 8-month dose-response randomized double-blind placebo-controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100,000 SQ-U, 10,000 SQ-U or placebo injections. Serum specimens were collected before treatment, after up-dosing, during the peak season and at the end of the study. Allergen-specific IgG(4) titres and IgG-associated inhibitory activity were evaluated., Results: A time- and dose-dependent increase in serum inhibitory activity for both the IgE-blocking factor and IgE-FAB was observed, which paralleled increases in grass pollen-specific IgG(4) antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom-rescue medication scores (IgE-FAB: r = -0.25, P = 0.0002; IgE-blocking factor: r = -0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG(4) levels (r = -0.11, P = 0.12)., Conclusions: Functional assays of inhibitory IgG(4) and IgE-blocking factor may be more useful surrogates of clinical response than IgG(4). Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation., (© 2011 John Wiley & Sons A/S.)

Specific allergen immunotherapy is clinically effective and disease modifying. It has a duration of effect that exceeds the treatment period and prevents both the progression of allergic rhinitis to asthma and the acquisition of new allergic sensitizations. However, immunotherapy is associated with a high frequency of adverse events related to the allergenicity of vaccines. Allergenicity is conferred by the presence of intact B-cell epitopes that crosslink allergen-specific IgE on effector cells. The use of linear peptide sequences representing fragments of the native allergen is one approach to reduce allergenicity. Preclinical models of peptide immunotherapy have demonstrated efficacy in both autoimmunity and allergy. Translation of this technology into the clinic has gained momentum in recent years based on encouraging results from early clinical trials. To date, efforts have focused on two major allergens, but vaccines to a broader range of molecules are currently in clinical development. Mechanistically, peptide immunotherapy appears to work through the induction of adaptive, allergen-specific regulatory T cells that secrete the immunoregulatory cytokine IL-10. There is also evidence that peptide immunotherapy targeting allergen-specific T cells can indirectly modulate allergen-specific B-cell responses. Peptide immunotherapy may provide a safe and efficacious alternative to conventional subcutaneous and/or sublingual approaches using native allergen preparations., (© 2011 John Wiley & Sons A/S.)

Because of the need to standardize allergen immunotherapy and the desire to reduce allergic adverse events during therapy, a transition to recombinant/synthetic hypoallergenic approaches is inevitable. Evidence supports the notion that effective therapy can be delivered using a limited panel of allergens or even epitopes, weakening the argument that all allergens must be present for optimal efficacy. Moreover, standardized products will allow direct comparisons between studies and, for the first time, immunotherapy studies will be truly blinded, allowing an accurate assessment of the actual treatment effect that can be achieved with this form of intervention., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Specific immunotherapy (SIT) with extracts containing intact allergen molecules is clinically efficacious, but associated with frequent adverse events related to the allergic sensitization of the patient. As a result, treatment is initiated in an incremental dose fashion which ultimately achieves a plateau (maintenance dose) that may be continued for several years. Reduction of allergic adverse events may allow safer and more rapid treatment Thus, many groups have developed and evaluated strategies to reduce allergenicity whilst maintaining immunogenicity, the latter being required to achieve specific modulation of the immune response. Peptide immunotherapy can be used to target T and/or B cells in an antigen-specific manner. To date, only approaches that target T cells have been clinically evaluated. Short, synthetic peptides representing immunodominant T cell epitopes of major allergens are able to modulate allergen-specific T cell responses in the absence of IgE cross linking and activation of effector cells. Here we review clinical and mechanistic studies associated with peptide immunotherapy targeting allergy to cats or to bee venom.

The use of synthetic peptide fragments of allergen molecules holds promise for the delivery of effective immunotherapy without IgE-mediated adverse events. Early studies were associated with frequent induction of allergic symptoms after treatment, mostly related to activation of allergen-specific effector T cells with high doses of peptides. More recently, low doses of peptides have been shown to modify clinical and laboratory surrogates without inducing adverse events. Studies are ongoing to define the optimal dose, dose interval, and route of administration. Current results indicate that treatment with peptides modulates the immune response by reducing T(H)2 responses to allergen and increasing IL-10 production and the activity of allergen-specific regulatory T cells. Further studies are required in larger numbers of subjects and with peptides derived from a variety of allergens.

Specific allergen immunotherapy has been widely practised for almost 100 years. Whilst this approach is disease-modifying and efficacious, the use of whole allergen preparations is associated with an unacceptably high prevalence of allergic adverse events during treatment. Many approaches to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity are under development. One such approach is the use of short synthetic peptides which represent major T-cell epitopes of the allergen. Major potential advantages of this approach include markedly reduced capacity to cross-link immunoglobulin-E and activate mast cells and basophils, and ease of manufacture and standardization. Promising results in preclinical studies have led to the translation of this approach to clinical studies in humans. Peptide immunotherapy is currently under development for allergic and autoimmune diseases.

T-cell responses to allergens are crucial in determining the choice between health and disease. Th2 responses drive synthesis of IgE and the recruitment, maturation, survival and effector function of accessory cells such as eosinophils, basophils and mast cells. Allergen-specific strategies for targeting T-cell responses in established allergic diseases have been employed with success for almost a century. Recently, new insight into the mechanism of action of such approaches has revealed modulation of the delicate and complex regulatory mechanisms including suppression of Th2 responses through antagonistic Th1 responses and regulation through IL-10 and TGFbeta production.

Allergen-specific immunotherapy has been carried out for almost a century and remains one of the few antigen-specific treatments for inflammatory diseases. The mechanisms by which allergen-specific immunotherapy exerts its effects include the modulation of both T-cell and B-cell responses to allergen. There is a strong rationale for improving the efficacy of allergen-specific immunotherapy by reducing the incidence and severity of adverse reactions mediated by IgE. Approaches to address this problem include the use of modified allergens, novel adjuvants and alternative routes of administration. This article reviews the development of allergen-specific immunotherapy, our current understanding of its mechanisms of action and its future prospects.

Synthetic peptides representing T-cell epitopes of allergens and autoantigens have been employed to induce antigen-specific tolerance in vivo in experimental models and the clinical setting. Delivery of peptides orally or by injection leads to reduced reactivity to antigen accompanied by the induction of T cells with a regulatory phenotype. Peptide therapy may provide a safe, effective, and economically viable approach for disease-modifying therapy in autoimmune and allergic diseases.

Background: We previously showed that overlapping Fel d 1-derived T-cell peptides inhibited surrogate markers of allergy (i.e. early and late-phase skin reactions and T-cell function) in cat allergic subjects. The present pilot study was designed to determine whether this treatment affected clinically relevant outcome measurements such as the allergen-induced nasal and bronchial reactions, and asthma/rhinitis quality of life (QOL)., Methods: Sixteen cat-allergic asthmatic subjects who gave a dual (early and late) asthmatic response (DAR) to inhaled cat allergen were randomly assigned to receive either Fel d 1 peptides (approximately 300 mug in increasing, divided doses) or placebo (8 active : 8 placebo). Twelve single early responders (SER) were also studied in an open fashion design. Allergen-induced bronchial and nasal measurements as well as the QOL was measured at baseline, 4-8 weeks (follow-up 1 (FU1)) and 3-4 months (FU2)., Results: In the active, but not placebo, group there were significant decreases in the late asthmatic reaction (LAR) to whole cat dander (P = 0.03) at FU2 but with no between group difference. There were also significant improvements in asthma quality of life (QOL) scores [asthma-activity limitation (P = 0.014); rhinitis-sleep (P = 0.024), non-nose/non-eye symptoms (P = 0.031), nasal problems (P = 0.015)]. In the open study Fel d 1 peptide treatment resulted in significant decreases in number of sneezes (P = 0.05), weight of nasal secretions (P = 0.04) and nasal blockage (P = 0.01) following allergen challenge., Conclusions: Multiple, short, overlapping Fel d 1 T-cell peptides have potential for inhibiting upper and lower airway outcome measurements in cat allergic patients. Larger, dose-ranging, studies are required before firm conclusions on clinical efficacy of peptide allergen therapy can be made.

Background: Specific immunotherapy with whole allergen extracts is associated with local accumulation of IFN-gamma+ and CD25+ cells indicating recruitment of activated T-helper type 1 (Th1) and/or T regulatory cells. We have studied allergen-induced, late-phase skin biopsies before and after T cell peptide therapy for evidence of alterations in the pattern of local recruitment of Th1, T-helper type 2 (Th2) and T regulatory cells., Objective: To evaluate the effect of T cell peptide therapy on the allergen-induced cutaneous late-phase reaction., Methods: Increasing doses of synthetic Fel d 1-derived peptides were administered (by intradermal injection) to eight cat-allergic asthmatics at 14-day intervals. Twenty-four-hour skin biopsies were taken from whole cat allergen- and diluent-injected sites, before and after treatment and studied by immunohistochemistry and in situ hybridization., Results: Fel-d 1 peptides decreased airway hyper-responsiveness (P = 0.02) and inhibited the late-phase cutaneous reaction (LPCR) to whole cat allergen (P = 0.03). This was associated with significant increases (post- vs. pre-treatment) in the number of cutaneous CD4+/IFN-gamma+ (P = 0.03) and CD4+/CD25+ cells (P = 0.04), but not in CD4+/IL-10+ or CD4+/CTLA-4+ cells., Conclusions: Treatment with allergen-derived T cell peptides results in allergen-dependent recruitment to the skin of Th1, rather than T regulatory cells, to cutaneous late-phase reaction sites.

Background: We have previously described both modification of allergen immunotherapy using peptide fragments, and reduced regulation of allergen stimulated T cells by CD4(+) CD25(+) T cells from allergic donors when compared with nonallergic controls. It has been suggested that allergen immunotherapy induces regulatory T cell activity: we hypothesized that allergen peptide immunotherapy might increase suppressive activity of CD4(+) CD25(+) T cells., Objective: To examine cat allergen-stimulated CD4 T cell responses and their suppression by CD4(+) CD25(+) T cells before and after cat allergen peptide immunotherapy in a double-blind placebo-controlled study., Methods: Peripheral blood was obtained and stored before and after peptide immunotherapy or placebo treatment. CD4(+) and CD4(+) CD25(+) were then isolated by immunomagnetic beads and cultured with allergen in vitro., Results: Comparing cells from blood taken before with that after peptide immunotherapy there was a significant reduction in both proliferation and IL-13 production by allergen-stimulated CD4+ T cells, whereas no change was seen after placebo. CD4(+) CD25(+) T cells suppressed both proliferation and IL-13 production by CD4(+) CD25(-) T cells before and after therapy but peptide therapy was not associated with any change in suppressive activity of these cells., Conclusion: Allergen peptide immunotherapy alters T cell response to allergen through mechanisms other than changes in CD4(+) CD25(+) T cell suppression.

Desensitising therapy for allergic diseases has changed little over almost a century of practice. Administration of increasing doses of extracts of allergen source material has been shown to be reproducibly effective when patients are carefully selected and appropriate concentrations of allergen employed. However, specific immunotherapy is limited by the interaction of specific IgE with allergen, leading to a relatively high frequency of adverse events including anaphylaxis and death. Several strategies have been developed to tackle this issue. Most of these rely on reducing the allergenicity of the treatment, whilst maintaining the immunogenicity. The use of short, synthetic peptide sequences corresponding to T-cell epitopes from the allergen has been shown to modify surrogate markers of allergy including cutaneous responses to allergen challenge and ex vivo parameters of T-cell activation. This review discusses recent advances in our understanding of the mechanisms and potential efficacy of this form of therapy.

Allergic conditions contribute significantly to the burden of chronic disease in the industrialized world. Current treatments offer varying degrees of palliation. The sole proven disease-modifying strategy, specific or whole-allergen immunotherapy, is limited because of the associated risk of systemic adverse effects, such as anaphylaxis. Short, linear allergen-derived peptides, corresponding to T cell epitopes, offer the possibility of a safer approach as they are capable of inducing allergen-specific hyporesponsiveness without cross-linking mast cell-bound IgE. This review evaluates the scientific basis of peptide immunotherapy and clinical experience in allergy up to the present time.

Conventional immunotherapy using whole allergen extracts has been shown to be an effective, disease-modifying treatment in carefully selected patients with allergic conjunctivo-rhinitis, asthma and bee and wasp venom hypersensitivity. However, this form of therapy is associated with the risk of systemic anaphylaxis, which, when severe, can be life threatening. A potentially significant reduction in the incidence of IgE-mediated events during immunotherapy may be achieved by the use of short peptides corresponding to T cell epitopes which, by virtue of their size, are incapable of cross-linking allergen-specific IgE bound to the surface of mast cells and basophils. Initial clinical studies have demonstrated degrees of efficacy which have, in some cases, been associated with adverse events occurring immediately or several hours after peptide administration. Preliminary data from studies employing shorter peptides (20 amino acids or less) suggest that improved efficacy may be achieved by using peptides of defined major histocompatibility complex-binding specificity administered in an incremental dose fashion comparable to conventional immunotherapy. This review will discuss the concept of peptide immunotherapy and the implications of recent studies., (Copyright 2000 S. Karger AG, Basel.)

The prevalence of atopic allergic disease increased substantially towards the end of the 20th century and is set to rise further. This group of diseases now constitutes the most common cause of chronic ill health in industrialised countries. Despite considerable attention from the pharmaceutical industry, little progress has been made in the development of disease-modifying therapies. In contrast, recent activity has focused almost exclusively on treatment of symptoms (palliation) rather than cause. The failure of palliative approaches to address the issue of increasing incidence of disease is in evidence in the case of allergic diseases and is a continuing focus of concern. At present, the most frequently employed non-palliative form of disease-modifying therapy is specific allergen immunotherapy (SIT) in which increasing doses of whole allergen extract are administered in increasing dose in order to desensitise the allergic subject.