Allergen-specific Immunotherapy (allergen-specific + immunotherapy)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Mechanisms of immune suppression by interleukin-10 and transforming growth factor-,: the role of T regulatory cells

IMMUNOLOGY, Issue 4 2006
Alison Taylor
Summary Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific type 1 regulatory (Tr1) cells and T helper (Th) 2 cells appears to be decisive in the development of allergy. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific interleukin-4 (IL-4)-secreting T cells in allergic individuals. Allergen-specific immunotherapy can induce specific Tr1 cells that abolish allergen-induced proliferation of Th1 and Th2 cells, as well as their cytokine production. Tr1 cells utilize multiple suppressor mechanisms, such as IL-10 and transforming growth factor-, (TGF-,) as secreted cytokines and various surface molecules, such as cytotoxic T-lymphocyte antigen 4 and programmed death-1. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors, which depend on CD28 costimulation. IL-10 inhibits CD28 tyrosine phosphorylation, preventing the binding of phosphatidylinositol 3-kinase p85 and consequently inhibiting the CD28 signalling pathway. In addition, IL-10 and TGF-, secreted by Tr1 cells skew the antibody production from immunoglobulin E (IgE) towards the non-inflammatory isotypes IgG4 and IgA, respectively. Induction of antigen-specific Tr1 cells can thus re-direct an inappropriate immune response against allergens or auto-antigens using a broad range of suppressor mechanisms. [source]


ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2010
U Darsow
Abstract Background, The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. Methods, EADV eczema task force developed its guideline for atopic dermatitis diagnosis and treatment based on literature review and repeated consenting group discussions. Results and Discussion, Basic therapy relies on hydrating topical treatment and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin antagonists is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the topical calcineurin inhibitors, tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial/antiseptic treatment. Systemic antihistamines (H1) can relieve pruritus, but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. ,Eczema school' educational programmes have been proven to be helpful. [source]


CD-sens: a biological measure of immunological changes stimulated by ASIT

ALLERGY, Issue 5 2009
A. Nopp
Background:, Allergen-specific immunotherapy (ASIT) in allergic rhinitis and asthma is the only treatment that effects the long-term development of these diseases. Basophil allergen threshold sensitivity, CD-sens, which is a valuable complement to resource-demanding clinical challenge tests, was used to monitor the initiation of ASIT induced allergen ,blocking activity'. Methods:, Patients IgE-sensitized to timothy (n = 14) or birch (n = 19) pollen were started on conventional (8,16 weeks) or ultra rush ASIT, respectively, and followed by measurements of CD-sens, allergen binding activity (ABA) and serum IgG4- and IgE-antibody concentrations. Results:, CD-sens decreased during the early phase of ASIT-treatment. In parallel, ABA increased and correlated significantly with the increasing levels of IgG4 antibody concentrations. High dosages of allergen were more effective while mode of dosing up did not seem to matter. No change was seen in basophil reactivity. Conclusion:, CD-sens and ABA, in contrast to basophil reactivity, seem to be promising tools to monitor protective immune responses initiated by ASIT. [source]


Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic review

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2008
Esther Röder
Allergen-specific immunotherapy is one of the cornerstones of allergic rhinoconjunctivitis treatment. Since the development of non-invasive administration forms with better safety profiles, there is an increasing tendency to prescribe immunotherapy in youngsters. However, no overview is available on the efficacy of immunotherapy in all its different administration forms in youngsters. Therefore, we systematically reviewed randomized controlled trials (RCTs) to evaluate the effect of immunotherapy with inhalant allergens on symptoms and medication use in children and adolescents with allergic rhinoconjunctivitis. Medline, EMBASE, the Cochrane Controlled Clinical Trials Register and reference lists of recent reviews and published trials were searched. RCTs including youngsters aged 0,18 yr with allergic rhinoconjunctivitis and comparing immunotherapy with placebo, symptomatic treatment or a different administration form of immunotherapy were included. Primary outcome measures were rhinoconjunctivitis symptom and/or medication scores. Methodological quality was assessed using the validated Delphi list. A method of best evidence synthesis, a rating system with levels of evidence based on the overall quality and the outcome of the trials, was used to assess efficacy. Six subcutaneous (SCIT), four nasal (LNIT), seven oral (OIT) and 11 sublingual (SLIT) immunotherapy trials, comprising 1619 youngsters, were included. Only 39% of the trials were of high methodological quality. For the SCIT and OIT subgroups the level of evidence for efficacy was conflicting. Moderate evidence of effect was found for LNIT. Analysis of the SLIT subgroup showed no evidence of effect. The evidence for the perennial and seasonal allergen trials within the subgroups varied from moderate evidence of effect to no evidence of effect. In conclusion, there is at present insufficient evidence that immunotherapy in any administration form has a positive effect on symptoms and/or medication use in children and adolescents with allergic rhinoconjunctivitis. [source]


Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin E and T cell reactivity

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2010
M. Focke
Summary Allergen-specific immunotherapy (SIT) is the only specific and disease-modifying approach for the treatment of allergy but several disadvantages have limited its broad applicability. We argue that the majority of the possible disadvantages of SIT such as unwanted effects, poor efficacy and specificity as well as inconvenient application are related to the poor quality of natural allergen extracts, which are the active ingredients of all currently available allergy vaccines. Because of the progress made in the field of molecular allergen characterization, new allergy vaccines based on recombinant allergens, recombinant hypoallergenic allergen derivatives and allergen-derived T cell peptides have entered clinical testing and hold promise to reduce the side-effects and to increase the specificity as well as the efficacy of SIT. Here, we present a refined immunotherapy concept, which is based on the use of peptides derived from allergen surfaces that exhibit reduced, allergen-specific IgE as well as T cell reactivity. These peptides when fused to non-allergenic carriers give rise to allergen-specific protective IgG responses with T cell help from a non-allergenic carrier molecule. We summarize the experimental data demonstrating that such peptide vaccines can bypass allergen-specific IgE as well as T cell activation and may be administered at high doses without IgE- and T cell-mediated side-effects. Should these peptide vaccines prove efficacious and safe in clinical trials, it may become possible to develop convenient, safe and broadly applicable forms of SIT as true alternatives to symptomatic, drug-based allergy treatment. Cite this as: M. Focke, I. Swoboda, K. Marth and R. Valenta, Clinical & Experimental Allergy, 2010 (40) 385,397. [source]


Toll-like receptor ligands as adjuvants in allergen-specific immunotherapy

CLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2005
P. Johansen
Summary Background Allergen-specific immunotherapy (SIT) leads to long-term amelioration of T-helper type 2 (Th2)-mediated allergic symptoms and is therefore recommended as a first line therapy for allergies. The major disadvantage of SIT is its low efficiency, requiring treatment over years. Objective In this study, we evaluated the potential of Toll-like receptor (TLR) ligands to facilitate Th1-type immune responses. Methods The immunogenicity and therapeutic potential of the major bee venom allergen phospholipase A2 (PLA2) combined with various TLR ligands were tested in mice and compared with immune responses induced by conventional aluminium-based preparations. Results Regarding total IgG against PLA2, TLR2/4-binding lipopolysaccharide and TLR3-binding polyriboinosinic polyribocytidylic (PolyI:C) were the superior adjuvants for prophylactic vaccination. However, TLR9-binding phosphorothioate-modified cytosine,guanosine-rich oligonucleotide (CpG), TLR-3-binding PolyI:C, and TLR2/6-binding peptidoglycan skewed the immune responses more towards IgG2a isotype and Th1 cytokines. Furthermore, in a therapeutic approach, CpG, PolyI:C and TLR7/8-binding 3M003 had immune modulating properties as they suppressed established IgE titres. Conclusion The potential of TLR ligands to adjuvate the immunogenicity of bee venom PLA2 and to skew the Th1,Th2 balance proved very heterogeneous. With respect to SIT, CpG, PolyI:C, and 3M003 were very promising. Hence, TLR ligands should be considered as adjuvants or immune modulators in SIT in human as to improve its efficiency regarding the Th1,Th2 balance of the immune response with a likely effect on therapy duration. [source]


T cell responses induced by allergen-specific immunotherapy

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2010
E. Maggi
Summary Allergen-specific immunotherapy is recognized as a highly effective practice in the treatment of patients with severe allergic rhinitis and/or asthma and is recommended by World Health Organization as an integrated part of allergy management strategy. Several studies have shown that allergen-specific immunotherapy, based on the administration of increasing doses of allergen, achieves a hyposensitization and reduces both early and late responses occurring during the natural exposure to the allergen itself. This is the unique antigen-specific immunomodulatory treatment in current use for human diseases. Successful immunotherapy is associated with reductions in symptoms and medication scores and improved quality of life. After interruption it usually confers long-term remission of symptoms and prevents the onset of new sensitizations in children up to a number of years. Subcutaneous immunotherapy usually suppresses the allergen-induced late response in target organs, likely due to the reduction of the infiltration of T cells, eosinophils, basophils, mast cells and neutrophils. In addition to the reduction of cells of allergic inflammation, immunotherapy also decreases inflammatory mediators at the site of allergen exposure. This review provides an update on the immunological T cell responses induced by conventional subcutaneous and sublingual immunotherapy, and gives a unifying view to reconciling the old dualism between immunoredirecting and immunoregulating mechanisms. [source]


The CONSORT statement checklist in allergen-specific immunotherapy: a GA2LEN paper

ALLERGY, Issue 12 2009
P. J. Bousquet
The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients' inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis. [source]


Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy

ALLERGY, Issue 1 2009
J. M. Martínez-Gómez
Background:, Current s.c. allergen-specific immunotherapy (SIT) leads to amelioration of IgE-mediated allergy, but it requires numerous allergen injections over several years and is frequently associated with severe side-effects. The aim of this study was to test whether modified recombinant allergens can improve therapeutic efficacy in SIT while reducing allergic side-effects. Methods:, The major cat allergen Fel d 1 was fused to a TAT-derived protein translocation domain and to a truncated invariant chain for targeting the MHC class II pathway (MAT-Fel d 1). The immunogenicity was evaluated in mice, while potential safety issues were assessed by cellular antigen stimulation test (CAST) using basophils from cat-dander-allergic patients. Results:, MAT-Fel d 1 enhanced induction of Fel d 1-specific IgG2a antibody responses as well as the secretion of IFN-, and IL-2 from T cells. Subcutaneous allergen-specific immunotherapy of mice using the modified Fel d 1 provided stronger protection against anaphylaxis than SIT with unmodified Fel d 1, and MAT-Fel d 1 caused less degranulation of human basophils than native Fel d 1. Conclusion:, MAT-Fel d 1 allergen enhanced protective antibody and Th1 responses in mice, while reducing human basophil degranulation. Immunotherapy using MAT-Fel d 1 allergen therefore has the potential to enhance SIT efficacy and safety, thus, shortening SIT. This should increase patient compliance and lower treatment costs. [source]


The functional insufficiency of human CD4+CD25high T-regulatory cells in allergic asthma is subjected to TNF-, modulation

ALLERGY, Issue 1 2008
Y.-L. Lin
Background:, Natural CD4+CD25highFoxp3+ regulatory T (nTreg) cells are important in maintaining immunologic tolerance, but their role in the pathogenesis of allergic asthma is unclear. We studied the function of nTreg cells in allergic asthmatic children and assessed the factors which may relate to the functional insufficiency of nTreg cells. Methods:, The percentage of CD4+CD25high Treg cells, the expression of Foxp3, and the cell-induced suppressive activity of nTreg cells isolated from nonatopic controls, allergic asthmatics, and allergen-specific immunotherapy (AIT)-treated asthmatic patients were studied. Results:, Although the percentage of nTreg in peripheral blood mononuclear cells was increased, the expression of Foxp3 and its cell-induced suppressive activity were significantly lower in Dermatophagoides pteronyssinus (Der p)-sensitive asthmatic children when compared to nonatopic controls. In contrast, the expression of Foxp3 and the functional activity of nTreg cells were reversed in allergic asthmatics who received AIT. The addition of recombinant tumor necrosis factor (TNF)-, directly downregulated Foxp3 expression and abrogated the cell-induced suppressive function of Treg cells. The anti-TNF-, reagent, etanercept, restored the functional activity and Foxp3 expression of CD4+CD25high Treg derived from allergic asthmatics. Conclusions:, The functional insufficiency of nTreg cells in patients with allergic asthma may be related to the enhanced production of TNF-, and its effect on the Foxp3 expression. These results may explain, in part, the effectiveness of anti-TNF-, therapy in the treatment of allergic asthma. [source]


Standards for practical allergen-specific immunotherapy

ALLERGY, Issue 2006
E. Alvarez-Cuesta
No abstract is available for this article. [source]


IgE reactivity to latex allergens among sensitized healthcare workers before and after immunotherapy with latex

ALLERGY, Issue 2 2006
J. Sastre
Background:, New IgE sensitizations to proteins in allergen extracts have been shown to occur during allergen-specific immunotherapy (IT). Methods:, Twenty-four healthcare workers (HCWs) , patients included in a latex IT study , were analysed, 16 in active treatment and eight in placebo. Sera were obtained at baseline and after 6 months of IT and analysed with immunoblotting and CAP System with eight single recombinant latex allergens (rHev b 1, 3, 5, 6.01, 8, 9, 10, 11, and a mix of rHev b1, 5, 6.01 and 8). Results:, After IT with latex, three patients in the active treatment group had new IgE sensitizations, one to Hev b 5, one to Hev b 11 and another to Hev b 6.01. No other significant variation in mean of specific IgE to latex or recombinant allergens were observed in patients who received placebo or active treatment. A significant (P = 0.012) negative correlation (,0.72) was observed between maximal tolerated dose and specific IgE to Hev b 6.01 at baseline. After IT, immunoblot analysis demonstrated a significant increase in IgE binding in a band of approximately 22 kDa (P = 0.032) that may correspond to Hev b 6.01. New or more intense bands appeared in seven patients of the active group, while in three subjects a reduction was observed. Conclusions:, Hev b 6.01 seems to be the most relevant latex allergen in HCWs. New or more intense IgE binding to latex allergenic components occurs during latex immunotherapy. However, the levels of specific IgE against these new components are low and do not seem to have clinical relevance. [source]


Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study

ALLERGY, Issue 1 2004
M. S. Khinchi
Background:, Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed. Objective:, To investigate the clinical efficacy of SLIT vs SCIT and secondary to compare SLIT and SCIT with placebo and to evaluate the relative clinical efficacy in relation to systemic side-effects. Methods:, A 3-year randomized, placebo-controlled, double-blind, double-dummy study including 71 adult birch pollen hay fever patients treated for two consecutive years after a baseline year. Allocation to treatment groups was based on disease severity in the baseline season, gender and age. Results:, Clinical efficacy was estimated in 58 patients completing the first treatment year by subtracting baseline data and by calculating the ratio first treatment season vs baseline. SLIT diminished the median disease severity to one-half and SCIT to one-third of placebo treatment. No statistical significant difference between the two groups was observed. Both for symptoms and medication scores actively treated patients showed statistically significant and clinical relevant efficacy compared with placebo. SLIT treatment only resulted in local mild side-effects, while SCIT resulted in few serious systemic side-effects. Conclusion:, Based on the limited number of patients the clinical efficacy of SLIT was not statistically different from SCIT, and both treatments are clinically effective compared with placebo in the treatment of birch pollen rhinoconjunctivitis. The lack of significant difference between the two treatments does not indicate equivalent efficacy, but to detect minor differences necessitates investigation of larger groups. Due to the advantageous safety profile SLIT may be favored. [source]


Clinical outcome and IL-17, IL-23, IL-27 and FOXP3 expression in peripheral blood mononuclear cells of pollen-allergic children during sublingual immunotherapy

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1-Part-II 2010
Kaisa Nieminen
Nieminen K, Valovirta E, Savolainen J. Clinical outcome and IL-17, IL-23, IL-27 and FOXP3 expression in peripheral blood mononuclear cells of pollen-allergic children during sublingual immunotherapy. Pediatr Allergy Immunol 2010: 21: e174,e184. © 2009 John Wiley & Sons A/S Induction of allergen-specific, tolerogenic, IL-10 and/or TGF-,-producing T-regulatory (Treg) cells that express transcription factor FOXP3 is considered as one of the key mechanisms of allergen-specific immunotherapy. However, little is known of the induction of FOXP3 expression in children during sublingual immunotherapy (SLIT). Recently, also, a novel subgroup of T-helper (Th) cells, the Th17 cells, secreting predominantly IL-17 (IL-17A), was identified. The expressions of IL-17 or the Th17-regulating cytokines IL-23 and IL-27 during SLIT are currently completely unexplored. This randomized, placebo-controlled dose-response study was performed to analyze the effects of SLIT on FOXP3, IL-17, IL-23, and IL-27 expressions in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis and their associations with clinical outcome. Thirty children were included: ten received SLIT with a glycerinated mixture of birch, hazel and alder with a cumulative weekly dose of 24,000 SQ-U, 10 with dose 200,000 SQ-U/wk, and ten received placebo. Cytokine and FOXP3 mRNA expressions in allergen-, purified protein derivative-stimulated and non-stimulated PBMC were determined at 0, 1 and 2 yr of SLIT by real-time RT-PCR (TaqMan®). Symptoms and medications were recorded using diary cards. Allergen-induced IL-17 mRNA expression was significantly increased in the study subjects with elevated combined Symptom Medication Score (SMS) after 2 yr. There was also a significant positive correlation between the allergen-induced IL-17 and SMS in whole study group (r = 0.38, p = 0.039) and especially the 200,000 SQ-U dose-treated group (r = 0.74, p = 0.027) at 2 yr. Allergen-induced FOXP3 mRNA expression was significantly increased in the 200,000 SQ-U dose-treated children after two study years as compared with baseline (p = 0.016) and placebo-treated children (p = 0.028). The changes in FOXP3 mRNA expression positively correlated with IL-10 and TGF-, mRNAs during SLIT in whole study population. Increased allergen-induced IL-17 responses during SLIT are associated with elevated SMS. Increased tolerogenic, allergen-specific Treg responses are also observed in children during SLIT. [source]


Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin E and T cell reactivity

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2010
M. Focke
Summary Allergen-specific immunotherapy (SIT) is the only specific and disease-modifying approach for the treatment of allergy but several disadvantages have limited its broad applicability. We argue that the majority of the possible disadvantages of SIT such as unwanted effects, poor efficacy and specificity as well as inconvenient application are related to the poor quality of natural allergen extracts, which are the active ingredients of all currently available allergy vaccines. Because of the progress made in the field of molecular allergen characterization, new allergy vaccines based on recombinant allergens, recombinant hypoallergenic allergen derivatives and allergen-derived T cell peptides have entered clinical testing and hold promise to reduce the side-effects and to increase the specificity as well as the efficacy of SIT. Here, we present a refined immunotherapy concept, which is based on the use of peptides derived from allergen surfaces that exhibit reduced, allergen-specific IgE as well as T cell reactivity. These peptides when fused to non-allergenic carriers give rise to allergen-specific protective IgG responses with T cell help from a non-allergenic carrier molecule. We summarize the experimental data demonstrating that such peptide vaccines can bypass allergen-specific IgE as well as T cell activation and may be administered at high doses without IgE- and T cell-mediated side-effects. Should these peptide vaccines prove efficacious and safe in clinical trials, it may become possible to develop convenient, safe and broadly applicable forms of SIT as true alternatives to symptomatic, drug-based allergy treatment. Cite this as: M. Focke, I. Swoboda, K. Marth and R. Valenta, Clinical & Experimental Allergy, 2010 (40) 385,397. [source]


The effect of oral steroids with and without vitamin D3 on early efficacy of immunotherapy in asthmatic children

CLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2009
P. Majak
Summary Background The possibility of additional strategies to enhance the effectiveness of specific immunotherapy (SIT) is highly attractive. Aim The aim of our study was to assess the influence of oral corticosteroids and oral corticosteroids combined with vitamin D3 on the early clinical and immunological effects of SIT. Methods It was a randomized, double-blind, placebo-controlled trial conducted in 54 asthmatic children allergic to house dust mites. Intervention was based on receiving a single dose of oral steroid, with or without vitamin D3, or placebo only on the day of the build-up phase of SIT. Results After 12 months of SIT, the median daily inhaled corticosteroid (ICS) dose, which controls the symptoms of asthma, was reduced by 25% in the steroid group. However, a 50% reduction of the median daily ICS dose was observed in the control group. The clinical effects of SIT were not affected in the steroid+D3 group. Concomitantly, we found that intervention with prednisone significantly impaired the induction of T regulatory lymphocytes. Importantly, the clinical and immunological effects of SIT were not affected by intervention with steroids administered with vitamin D3. Conclusions Our study failed to show a beneficial effect of oral corticosteroids on allergen-specific immunotherapy. We observed that the combined administration of a corticosteroid drug and allergen extract suppressed the early clinical and immunological effects of SIT and that vitamin D3 prevented this ,adverse' influence of steroids. [source]


Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial

CLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2009
G. Senti
Summary Background B-type CpG oligodeoxynucleotides (ODN) is currently used in clinical trials because of its prolonged half,life, which is due to its phosphorothioate backbone. A-type CpG ODN is a stronger inducer of IFN but has an unstable phosphodiester backbone that has so far prohibited its clinical use. However, upon association with virus-like particles (VLP) consisting of the bacteriophage Q, coat protein, A-type CpG ODN can be stabilized and can become an efficient adjuvant in mice. Therefore, the phase I/IIa study presented represents the first test of A-type CpGs in humans. Objective To test the safety, tolerability and clinical efficacy of QbG10 as an adjuvant for subcutaneous immunotherapy with a house dust mite (HDM) allergen extract in allergic patients. Methods A single centre, open-label phase I/IIa study evaluated the safety, tolerability and clinical efficacy of QbG10 as an adjuvant to immunotherapy with a subcutaneous HMD allergen extract in 20 patients suffering from HDM allergy. Twenty-one patients were enrolled between March and July 2005. Individual immunotherapy lasted 10 weeks. Clinical end-points included questionnaires, conjunctival provocation, skin prick tests and the measurement of allergen-specific IgG and IgE. Results QbG10 was well tolerated. Almost complete tolerance to the allergen was observed in conjunctival provocation testing after treatment with QbG10, and symptoms of rhinitis and allergic asthma were significantly reduced. Within 10 weeks of therapy, patients were nearly symptom-free and this amelioration lasted for at least 38 weeks post-treatment. Following injections of QbG10 and HDM allergen extract, allergen-specific IgG increased, while there was a transient increase in allergen-specific IgE titres. Skin reactivity to HDM was reduced. Conclusion The subcutaneous application of HDM allergen, together with A-type CpG ODN packaged into VLP, was safe. All patients achieved practically complete alleviation of allergy symptoms after 10 weeks of immunotherapy. This promising clinical outcome calls for larger placebo-controlled phase II studies. [source]


Side-effects of allergen-specific immunotherapy.

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2006
A prospective multi-centre study
Summary Background and objective The safety of allergen-specific immunotherapy (SIT) is a parameter of great interest in the overall assessment of the treatment. A clinical database was developed in order to obtain early warnings of changes in the frequency and severity of side-effects and sufficient data for the evaluation of possible risk factors. Methods During a 3-year period, four allergy centres in Copenhagen, Denmark, included data from all patients initiating SIT to a common database. Information on initial allergic symptoms, allergens used for treatment, treatment regimens and systemic side-effects (SSEs) during the build-up phase was collected. Results A total of 1038 patients received treatment with 1709 allergens (timothy, birch, mugwort, house dust mite (HDM), cat, and wasp and bee venom), 23 047 injections in total. Most SIT patients completed the updosing phase without side-effects, but there was a significant difference between allergens: wasp (89%), birch (82%), HDM (81%), cat (74%) and grass (70%) (P=0.004). A total of 582 SSEs were registered in 341 patients. Most side-effects were mild grade 2 reactions (78%). A difference in severity between allergens was observed (P=0.02), with grass giving most problems. The type of allergen but not patient- or centre-related parameters seemed predictive of side-effects. Conclusions Allergen extracts differ in their tendency to produce side-effects. Multi-centre studies like the present one allow more patients to be evaluated, and thereby provide a more efficient surveillance of side-effects. Online Internet-based registration to a central national database of every allergen injection would be an even more powerful tool for evaluation of risk factors and surveillance of side-effects. [source]


Toll-like receptor ligands as adjuvants in allergen-specific immunotherapy

CLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2005
P. Johansen
Summary Background Allergen-specific immunotherapy (SIT) leads to long-term amelioration of T-helper type 2 (Th2)-mediated allergic symptoms and is therefore recommended as a first line therapy for allergies. The major disadvantage of SIT is its low efficiency, requiring treatment over years. Objective In this study, we evaluated the potential of Toll-like receptor (TLR) ligands to facilitate Th1-type immune responses. Methods The immunogenicity and therapeutic potential of the major bee venom allergen phospholipase A2 (PLA2) combined with various TLR ligands were tested in mice and compared with immune responses induced by conventional aluminium-based preparations. Results Regarding total IgG against PLA2, TLR2/4-binding lipopolysaccharide and TLR3-binding polyriboinosinic polyribocytidylic (PolyI:C) were the superior adjuvants for prophylactic vaccination. However, TLR9-binding phosphorothioate-modified cytosine,guanosine-rich oligonucleotide (CpG), TLR-3-binding PolyI:C, and TLR2/6-binding peptidoglycan skewed the immune responses more towards IgG2a isotype and Th1 cytokines. Furthermore, in a therapeutic approach, CpG, PolyI:C and TLR7/8-binding 3M003 had immune modulating properties as they suppressed established IgE titres. Conclusion The potential of TLR ligands to adjuvate the immunogenicity of bee venom PLA2 and to skew the Th1,Th2 balance proved very heterogeneous. With respect to SIT, CpG, PolyI:C, and 3M003 were very promising. Hence, TLR ligands should be considered as adjuvants or immune modulators in SIT in human as to improve its efficiency regarding the Th1,Th2 balance of the immune response with a likely effect on therapy duration. [source]


T cell responses induced by allergen-specific immunotherapy

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2010
E. Maggi
Summary Allergen-specific immunotherapy is recognized as a highly effective practice in the treatment of patients with severe allergic rhinitis and/or asthma and is recommended by World Health Organization as an integrated part of allergy management strategy. Several studies have shown that allergen-specific immunotherapy, based on the administration of increasing doses of allergen, achieves a hyposensitization and reduces both early and late responses occurring during the natural exposure to the allergen itself. This is the unique antigen-specific immunomodulatory treatment in current use for human diseases. Successful immunotherapy is associated with reductions in symptoms and medication scores and improved quality of life. After interruption it usually confers long-term remission of symptoms and prevents the onset of new sensitizations in children up to a number of years. Subcutaneous immunotherapy usually suppresses the allergen-induced late response in target organs, likely due to the reduction of the infiltration of T cells, eosinophils, basophils, mast cells and neutrophils. In addition to the reduction of cells of allergic inflammation, immunotherapy also decreases inflammatory mediators at the site of allergen exposure. This review provides an update on the immunological T cell responses induced by conventional subcutaneous and sublingual immunotherapy, and gives a unifying view to reconciling the old dualism between immunoredirecting and immunoregulating mechanisms. [source]