Side‐effects of allergen‐specific immunotherapy. A prospective multi‐centre study

Winther, Lone; Arnved, J.; Malling, Hans‐Jørgen; Nolte, Hendrik; Mosbech, H.

doi:10.1111/j.1365-2222.2006.02340.x

Cited by 120 publications

(91 citation statements)

References 12 publications

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“…Natural allergen extracts are prepared directly from the raw allergen sources and, if not modified, contain allergenic material. The injection or mucosal administration (SLIT) of allergen extracts can therefore induce a variety of side-effects ranging from local side-effects to severe systemic side-effects, which in the worst case may be life-threatening reactions [33][34][35][36]. The sublingual forms of treatment show a lower rate of side-effects than injection immunotherapy.…”

Section: Factors Limiting the Broad Application Of Allergen-specific mentioning

confidence: 99%

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

Focke

Swoboda

Marth

et al. 2010

Clin Experimental Allergy

101

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SummaryAllergen-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.

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Section: Factors Limiting the Broad Application Of Allergen-specific mentioning

confidence: 99%

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

Focke

Swoboda

Marth

et al. 2010

Clin Experimental Allergy

101

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“…Airway hyperreactivity was assessed on day 29 by measurement of Penh (enhanced pause) by whole-body plethysmography (Buxco, Winchester, U.K.) as described previously (30). Mice were positioned in calibrated aerosol exposure chambers, exposed to increasing concentrations of methacholine (8,16,32, 64 mg/ml), and Penh was recorded.…”

Section: Development Of a Murine Model For The Treatment Of Grass Polmentioning

confidence: 99%

“…However, a major disadvantage of SIT is the risk for inducing side effects in the treated patients, which may be life-threatening when anaphylactic reactions develop. Severe negative side effects have been reported in particular for grass pollen immunotherapy (8). Another problem related to allergen extract-based SIT is that important allergens are not present in sufficient quantities in the allergen extract or induce low or no protective immune responses (9,10).…”

mentioning

confidence: 99%

Molecular Evolution of Hypoallergenic Hybrid Proteins for Vaccination against Grass Pollen Allergy

Linhart

Focke‐Tejkl

Weber

et al. 2015

The Journal of Immunology

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More than 10% of the population in Europe and North America suffer from IgE-associated allergy to grass pollen. In this article, we describe the development of a vaccine for grass pollen allergen-specific immunotherapy based on two recombinant hypoallergenic mosaic molecules, designated P and Q, which were constructed out of elements derived from the four major timothy grass pollen allergens: Phl p 1, Phl p 2, Phl p 5, and Phl p 6. Seventeen recombinant mosaic molecules were expressed and purified in Escherichia coli using synthetic genes, characterized regarding biochemical properties, structural fold, and IgE reactivity. We found that depending on the arrangement of allergen fragments, mosaic molecules with strongly varying IgE reactivity were obtained. Based on an extensive screening with sera and basophils from allergic patients, two hypoallergenic mosaic molecules, P and Q, incorporating the primary sequence elements of the four grass pollen allergens were identified. As shown by lymphoproliferation experiments, they contained allergen-specific T cell epitopes required for tolerance induction, and upon immunization of animals induced higher allergen-specific IgG Abs than the wild-type allergens and a registered monophosphoryl lipid A–adjuvanted vaccine based on natural grass pollen allergen extract. Moreover, IgG Abs induced by immunization with P and Q inhibited the binding of patients’ IgE to natural allergens from five grasses better than IgG induced with the wild-type allergens or an extract-based vaccine. Our results suggest that vaccines based on the hypoallergenic grass pollen mosaics can be used for immunotherapy of grass pollen allergy.

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“…IgE reactivity of rPhl p 2 and the rPhl p 2 mosaic. Nitrocellulose-dotted rPhl p 2 and rPhl p 2 mosaic, as well as HSA, were probed with sera from 12 grass pollen allergic patients (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Bound IgE Abs were detected with 125 I-labeled anti-human IgE Abs and visualized by autoradiography.…”

Section: Construction and Molecular Characterization Of A Recombinantmentioning

confidence: 99%

“…It can prevent the progression of allergic disease from mild (e.g., rhinoconjunctivitis) to severe manifestations (e.g., asthma) and has a long-lasting effect (10,11). However, the broad application of SIT has been limited by side effects caused by the administration of allergenic materials and the poor quality of natural allergen extracts (12). Due to the advances made in the field of allergen characterization through the application of recombinant DNA technology, DNAs coding for the most relevant allergens have become available and the corresponding allergens can now be produced as recombinant proteins equaling their natural counterparts (13).…”

mentioning

confidence: 99%

Disruption of Allergenic Activity of the Major Grass Pollen Allergen Phl p 2 by Reassembly as a Mosaic Protein

Mothes‐Luksch

Stumvoll

Linhart

et al. 2008

The Journal of Immunology

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The recognition of conformational epitopes on respiratory allergens by IgE Abs is a key event in allergic inflammation. We report a molecular strategy for the conversion of allergens into vaccines with reduced allergenic activity, which is based on the reassembly of non-IgE-reactive fragments in the form of mosaic proteins. This evolution process is exemplified for timothy grass pollen-derived Phl p 2, a major allergen for more than 200 million allergic patients. In a first step, the allergen was disrupted into peptide fragments lacking IgE reactivity. cDNAs coding for these peptides were reassembled in altered order and expressed as a recombinant mosaic molecule. The mosaic molecule had lost the three-dimensional structure, the IgE reactivity, and allergenic activity of the wild-type allergen, but it induced high levels of allergen-specific IgG Abs upon immunization. These IgG Abs crossreacted with group 2 allergens from other grass species and inhibited allergic patients’ IgE binding to the wild-type allergen. The mosaic strategy is a general strategy for the reduction of allergenic activity of protein allergens and can be used to convert harmful allergens into safe vaccines.

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Side‐effects of allergen‐specific immunotherapy. A prospective multi‐centre study

Cited by 120 publications

References 12 publications

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

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

Molecular Evolution of Hypoallergenic Hybrid Proteins for Vaccination against Grass Pollen Allergy

Disruption of Allergenic Activity of the Major Grass Pollen Allergen Phl p 2 by Reassembly as a Mosaic Protein

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