Non‐anaphylactic surface‐exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination

Focke, M.; Linhart, Birgit; Hartl, Arnulf; Wiedermann, Ursula; Sperr, Wolfgang R.; Valent, Peter; Thalhamer, Josef; Kraft, Dietrich; Valenta, Rudolf

doi:10.1111/j.1365-2222.2004.02081.x

Cited by 81 publications

(105 citation statements)

References 37 publications

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“…Rabbit anti-Bet v 1, anti-P2, and anti-P6 Abs have been described and were affinity purified using protein G (Pierce, Rockford, IL) (26).…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we generated and identified mouse mAbs that were specific for two synthetic Bet v 1-derived peptides (peptide comprising aa 29-58 [P2] and aa 73-103 [P6]), which, after immunization of rabbits, had induced Abs that inhibited IgE binding to Bet v 1 almost as good as rabbit Abs raised against the complete Bet v 1 allergen (26). The mouse mAbs were used for the mapping of the epitopes recognized by allergic patients' IgE using competitive binding assays.…”

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confidence: 99%

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Mapping of Conformational IgE Epitopes with Peptide-Specific Monoclonal Antibodies Reveals Simultaneous Binding of Different IgE Antibodies to a Surface Patch on the Major Birch Pollen Allergen, Bet v 1

Gieras

Cejka

Blatt

et al. 2011

The Journal of Immunology

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Allergic inflammation is based on the cross-linking of mast cell and basophil-bound IgE Abs and requires at least two binding sites for IgE on allergens, which are difficult to characterize because they are often conformational in nature. We studied the IgE recognition of birch pollen allergen Bet v 1, a major allergen for >100 million allergic patients. Monoclonal and polyclonal Abs raised against Bet v 1-derived peptides were used to compete with allergic patients’ IgE binding to Bet v 1 to search for sequences involved in IgE recognition. Strong inhibitions of patients’ IgE binding to Bet v 1 (52–75%) were obtained with mAbs specific for two peptides comprising aa 29–58 (P2) and aa 73–103 (P6) of Bet v 1. As determined by surface plasmon resonance, mAb2 specific for P2 and mAb12 specific for P6 showed high affinity, but only polyclonal rabbit anti-P2 and anti-P6 Abs or a combination of mAbs inhibited allergen-induced basophil degranulation. Thus, P2 and P6 define a surface patch on the Bet v 1 allergen, which allows simultaneous binding of several different IgE Abs required for efficient basophil and mast cell activation. This finding explains the high allergenic activity of the Bet v 1 allergen. The approach of using peptide-specific Abs for the mapping of conformational IgE epitopes on allergens may be generally applicable. It may allow discriminating highly allergenic from less allergenic allergen molecules and facilitate the rational design of active and passive allergen-specific immunotherapy strategies.

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“…Rabbit anti-Bet v 1, anti-P2, and anti-P6 Abs have been described and were affinity purified using protein G (Pierce, Rockford, IL) (26).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Mapping of Conformational IgE Epitopes with Peptide-Specific Monoclonal Antibodies Reveals Simultaneous Binding of Different IgE Antibodies to a Surface Patch on the Major Birch Pollen Allergen, Bet v 1

Gieras

Cejka

Blatt

et al. 2011

The Journal of Immunology

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“…The peptide vaccines contain unfolded allergen-derived peptides, which represent only a relatively small percentage of the allergen-derived sequences and lack most T cell epitopes. It is, therefore, expected that these vaccines will not boost the allergen-specific IgE responses, an assumption, which is supported by data from animal immunization experiments [117]. Immunotherapy trials are now needed to deliver the proof of concept in patients, to demonstrate whether the by-passing of allergen-derived T cell epitopes is not a disadvantage, to study clinical efficacy and to confirm the lack of any side-effects.…”

Section: Outlook Visions and Possible Advantages Of The Peptide Vaccmentioning

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

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100

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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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“…Antigen-specific rabbit IgG antibodies were developed with a 1:2,000 dilution of donkey anti-rabbit IgG peroxidase-coupled antibodies (Amersham Biosciences, Europe, Freiburg, Germany). Binding was quantified at 405 nm and 490 nm for rabbit antibodies and at 405 nm and 450 nm for mice antibodies in an ELISA reader (Dynatech, Denkendorf, Germany) [35,37].…”

Section: Construction Of Expression Vectors Harbouring the Vp1 Cdna Omentioning

confidence: 99%

Antibodies induced with recombinant VP1 from human rhinovirus exhibit cross-neutralisation

Edlmayr¹,

Niespodziana²,

Popow‐Kraupp³

et al. 2010

European Respiratory Journal

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Human rhinoviruses (HRVs) are the major cause of the common cold and account for 30-50% of all acute respiratory illnesses. Although HRV infections are usually harmless and invade only the upper respiratory tract, several studies demonstrate that HRV is involved in the exacerbation of asthma.VP1 is one of the surface-exposed proteins of the viral capsid that is important for the binding of rhinoviruses to the corresponding receptors on human cells. Here we investigated its potential usefulness for vaccination against the common cold.We expressed VP1 proteins from two distantly related HRV strains, HRV89 and HRV14, in Escherichia coli. Mice and rabbits were immunised with the purified recombinant proteins.The induced antibodies reacted with natural VP1 and with whole virus particles as shown by immunoblotting and immunogold electron microscopy. They exhibited strong cross-neutralising activity for different HRV strains. Therefore, recombinant VP1 may be considered a candidate HRV vaccine to prevent HRV-induced asthma exacerbations.

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Non‐anaphylactic surface‐exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination

Abstract: Our results indicate the mechanistic importance of blocking antibodies for allergy vaccination and present a B cell epitope-based approach for the rational design of safe peptide allergy vaccines whenever the structure of the disease-eliciting allergen is known.

Cited by 81 publications

References 37 publications

Mapping of Conformational IgE Epitopes with Peptide-Specific Monoclonal Antibodies Reveals Simultaneous Binding of Different IgE Antibodies to a Surface Patch on the Major Birch Pollen Allergen, Bet v 1

Mapping of Conformational IgE Epitopes with Peptide-Specific Monoclonal Antibodies Reveals Simultaneous Binding of Different IgE Antibodies to a Surface Patch on the Major Birch Pollen Allergen, Bet v 1

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

Antibodies induced with recombinant VP1 from human rhinovirus exhibit cross-neutralisation

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