Vaccination with genetically engineered allergens prevents progression of allergic disease

Niederberger, Verena; Horak, Friedrich; Vrtala, Susanne; Spitzauer, Susanne; Krauth, Maria‐Theresa; Valent, Peter; Reisinger, Jürgen; Pelzmann, M.; Hayek, Brigitte; Kronqvist, Malin; Gafvelin, Guro; Grönlund, Hans; Purohit, Ashok; Suck, Roland; Fiebig, Helmut; Cromwell, Oliver; Pauli, G.; Hage, Marianne van; Valenta, Rudolf

doi:10.1073/pnas.0404735101

Cited by 331 publications

(339 citation statements)

References 32 publications

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“…The presence of conformational B cell epitopes proposed a novel approach to reduce IgE binding by fragmentation [24] and oligomerization of one allergen or hybridization of several allergens [25,26]. The majority of Ab elicited by exposure to native protein antigens recognize conformation-dependent, discontinuous epitopes [2,12,27], which is confirmed using mouse mAb against Api m 1 and Api m 2.…”

Section: Discussionmentioning

confidence: 93%

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

Karamloo¹,

Schmid‐Grendelmeier

Kussebi³

et al. 2005

Eur. J. Immunol.

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Novel approaches for the prevention of allergy are required, because of the inevitably increasing prevalence of allergic diseases during the last 30 years. Here, a recombinant chimeric protein, which comprises the whole amino acid sequences of three bee venom major allergens has been engineered and used in prevention of bee venom sensitization in mice. Phospholipase A 2 (Api m 1), hyaluronidase (Api m 2) and melittin (Api m 3) fragments with overlapping amino acids were assembled in a different order in the Api m (1/2/3) chimeric protein, which preserved entire T cell epitopes, whereas B cell epitopes of all three allergens were abrogated. Accordingly, IgE cross-linking leading to mast cell and basophil mediator release was profoundly reduced in humans. Supporting these findings, the Api m (1/2/3) induced 100 to 1000 times less type-1 skin test reactivity in allergic patients. Treatment of mice with Api m (1/2/3) led to a significant reduction of specific IgE development towards native allergen, representing a protective vaccine effect in vivo. These results demonstrate a novel prototype of a preventive allergy vaccine, which preserves the entire T cell epitope repertoire, but bypasses induction of IgE against native allergen, and side effects related to mast cell/basophil IgE FceRI cross-linking in sensitized individuals.

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Section: Discussionmentioning

confidence: 93%

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

Karamloo¹,

Schmid‐Grendelmeier

Kussebi³

et al. 2005

Eur. J. Immunol.

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“…41 The use of allergen extracts brings forth the possibility of de novo sensitization against natural allergen components delivered in allergen extract preparations. Alternatively, using the allergen in recombinant form, [42][43][44] or only the major T-cell epitopes, 12,45 has enhanced treatment efficacy and safety. Additionally, peptide immunotherapy using peptides against multiple immunodominant allergen-specific T-cell epitopes is a safe and promising strategy for allergy control.…”

Section: Antigen Dose and Formulationmentioning

confidence: 99%

Strategies of mucosal immunotherapy for allergic diseases

Chuang

Chiang

2011

Cell Mol Immunol

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Incidences of allergic disease have recently increased worldwide. Allergen-specific immunotherapy (SIT) has long been a controversial treatment for allergic diseases. Although beneficial effects on clinically relevant outcomes have been demonstrated in clinical trials by subcutaneous immunotherapy (SCIT), there remains a risk of severe and sometimes fatal anaphylaxis. Mucosal immunotherapy is one advantageous choice because of its non-injection routes of administration and lower side-effect profile. This study reviews recent progress in mucosal immunotherapy for allergic diseases. Administration routes, antigen quality and quantity, and adjuvants used are major considerations in this field. Also, direct uses of unique probiotics, or specific cytokines, have been discussed. Furthermore, some researchers have reported new therapeutic ideas that combine two or more strategies. The most important strategy for development of mucosal therapies for allergic diseases is the improvement of antigen formulation, which includes continuous searching for efficient adjuvants, collecting more information about dominant T-cell epitopes of allergens, and having the proper combination of each. In clinics, when compared to other mucosal routes, sublingual immunotherapy (SLIT) is a preferred choice for therapeutic administration, although local and systemic side effects have been reported. Additionally, not every allergen has the same beneficial effect. Further studies are needed to determine the benefits of mucosal immunotherapy for different allergic diseases after comparison of the different administration routes in children and adults. Data collected from large, well-designed, double-blind, placebo-controlled, and randomized trials, with post-treatment follow-up, can provide robust substantiation of current evidence.

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“…During the past 20 decades an impressive number of allergens from different sources have been cloned, sequenced, produced as recombinant proteins, and partly evaluated for their diagnostic [10], and therapeutic value [12,13]. Behind plant pollens and mites with 184 and 164 reported single allergens, respectively, fungi with 100 allergens represent the third group of organisms from where the largest number of allergens has been cloned and characterised ( Table 1).…”

Section: The World Of Fungal Allergensmentioning

confidence: 99%

“…The use of recombinant allergens for allergen-specific immunotherapy is claimed to solve problems related to the standardisation of extracts [72,73]. Indeed some studies report the successful immunotherapy of pollen allergic patients with recombinant allergens [12,[74][75][76]. Therefore, the use of recombinant allergens for the immunotherapy of fungal allergies may be a future aim [1].…”

Section: Therapy Of Fungal Allergymentioning

confidence: 99%

Overview of Aspergillus Allergens

Crameri¹,

Glaser²,

Vilhelmsson

et al. 2009

Aspergillosis: From Diagnosis to Prevention

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Fungi in general and, Aspergillus fumigatus (A. fumigatus) in particular, are able to produce complex patterns of IgE-binding molecules. Robotics-based high throughput screening of A. fumigatus cDNA libraries displayed on phage surfaces revealed at last 81 different sequences encoding structures potentially able to bind to serum IgE of sensitised individuals suffering from A. fumigatus-related complications. Although not all of these allergens have been characterised in detail, A. fumigatus still represents the best investigated allergenic source. A total of 23 A. fumigatus allergens are recorded by the official allergen list of the International Union of Immunological Societies ( www.allergen.org ) and this is by far the longest allergen list reported for a single allergenic source. The IgE-binding molecules include species-specific as well as phylogenetically highly conserved cross-reactive structures and such with unknown function. A subset of cDNAs have been used to produce and characterise the corresponding recombinant allergens which have proven to be useful diagnostic reagents allowing specific detection of A. fumigatus sensitisation and differential diagnosis of allergic bronchopulmonary aspergillosis. Structures highly conserved through different species like manganese-dependent superoxide dismutase, P 2 acidic ribosomal protein, cyclophilins and thioredoxins induce, beyond sensitisation, IgE antibodies able to cross-react with the corresponding homologous self-antigens. The frequently observed cross-reactivity is traceable back to shared discontinuous B-cell epitopes as shown by detailed analyses of the crystal structures.

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Vaccination with genetically engineered allergens prevents progression of allergic disease

Cited by 331 publications

References 32 publications

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

Strategies of mucosal immunotherapy for allergic diseases

Overview of Aspergillus Allergens

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