Prevention of allergen‐specific IgE production and suppression of an established Th2‐type response by immunization with DNA encoding hypoallergenic allergen derivatives of Bet v 1, the major birch‐pollen allergen

IgE-mediated allergy to fish is a frequent cause of severe anaphylactic reactions. Parvalbumin, a small calcium-binding protein, is the major fish allergen. We have recently isolated a cDNA coding for carp parvalbumin, Cyp c 1, and expressed in Escherichia coli a recombinant Cyp c 1 molecule, which contained most IgE epitopes of saltwater and freshwater fish. In this study, we introduced mutations into the calcium-binding domains of carp parvalbumin by site-directed mutagenesis and produced in E. coli three parvalbumin mutants containing amino acid exchanges either in one (single mutants; Mut-CD and Mut-EF) or in both of the calcium-binding sites (double mutant; Mut-CD/EF). Circular dichroism analyses of the purified derivatives and the wild-type allergen showed that Mut-CD/EF exhibited the greatest reduction of overall protein fold. Dot blot assays and immunoblot inhibition experiments performed with sera from 21 fish-allergic patients showed that Mut-CD/EF had a 95% reduced IgE reactivity and represented the derivative with the least allergenic activity. The latter was confirmed by in vitro basophil histamine release assays and in vivo skin prick testing. The potential applicability for immunotherapy of Mut-CD/EF was demonstrated by the fact that mouse IgG Abs could be raised by immunization with the mutated molecule, which cross-reacted with parvalbumins from various fish species and inhibited the binding of fish-allergic patients’ IgE to the wild-type allergen. Using the hypoallergenic carp parvalbumin mutant Mut-CD/EF, it may be possible to treat fish allergy by immunotherapy.

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“…30), where the capability of Cyp c 1-specific IgE Abs to induce degranulation of RBL cells after contact with Cyp c 1 was analyzed.…”

Section: Immunization Of Mice and Determination Of Ag-specific Igg1 Amentioning

confidence: 99%

A Recombinant Hypoallergenic Parvalbumin Mutant for Immunotherapy of IgE-Mediated Fish Allergy

Swoboda

Bugajska-Schretter²,

Linhart

et al. 2007

The Journal of Immunology

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162

125

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“…Among them, Bet v 1, the major allergen of birch pollen, belongs to the most extensively studied molecules [9,15,16,17,18]. These studies have demonstrated that DNA-based immunization with a construct encoding Bet v 1 mounted Th1-biased specific immune responses and protected against allergic sensitization.…”

Section: Th1-biased Immunity – the Key To Dna-based Allergy Vaccinationmentioning

confidence: 93%

“…Neither blocking antibodies nor T regulatory cells or other tolerance-related responses play a major role in effective protective and therapeutic antiallergic DNA-based reactions [9]. …”

Section: Th1-biased Immunity – the Key To Dna-based Allergy Vaccinationmentioning

confidence: 99%

Is Genetic Vaccination against Allergy Possible?

Weiss

Scheiblhofer

Gabler

et al. 2006

Int Arch Allergy Immunol

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Genetic immunization has proven a powerful method to induce antiallergic immune responses. The underlying functional principle has been described to be based on the recruitment of allergen-specific Th1 cells, CD8+ cells and the establishment of a Th1 cytokine milieu, which prevent the development of a Th2-biased response in a protective setup and can balance an ongoing Th2-type response in a therapeutic situation. Genetic immunization with plasmid DNA offers innovative solutions to the major problems associated with protein immunization, such as crosslinking of pre-existing immunoglobulin E on mast cells/basophils or induction of de novo synthesis of immunoglobulin E by the protein immunization itself. It easily enables the routine production of hypoallergenic vaccines, which do not translate native allergens, thus avoiding potential anaphylactic side effects. DNA vaccines can also be applied as mixtures of single vaccines, making them interesting candidates for treatment based on component-resolved diagnosis, followed by an individualized therapy with the relevant allergens. In addition to the description of up-to-date allergen gene vaccine approaches, this review gives an overview of animal studies dealing with the following topics: danger signals as the inherent adjuvant properties, methods to optimize the vaccine immunogenicity, modulation of the immune response, nonparenteral applications and low-dose vaccination strategies.

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“…Allergens that are chemically coupled to virus-like particles [65,66] Genetic vaccines DNA vaccines -Vaccination with allergen-encoding DNA [88][89][90][91][92][93] RNA vaccines -Vaccination with allergen-encoding RNA [94] B. Alternative routes Sublingual -Sublingual administration of allergen-containing drops or tablets [17,24,[74][75][76][77][78][79] Oral -Oral administration of allergens (i.e.…”

Section: Coupled Allergensmentioning

confidence: 99%

“…The advantage of using allergen-encoding DNA instead of allergen for vaccination is, however, outweighed by the concern that genetic immunization may induce an uncontrolled production of allergens in treated subjects and thus may cause side effects [92]. To overcome this problem, genetic vaccination with DNA coding for hypoallergens has been considered as an alternative approach [93]. Furthermore, RNA immunization that gives rise to only transient allergen production has been considered as a possible alternative [94].…”

Section: Genetic Immunizationmentioning

confidence: 99%

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

Valenta

Campana

Marth

et al. 2012

Journal of Internal Medicine

101

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Immunoglobulin E-mediated allergies affect more than 25% of the population. Allergen exposure induces a variety of symptoms in allergic patients, which include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life-threatening systemic anaphylaxis. At present, allergen-specific immunotherapy (SIT), which is based on the administration of the disease-causing allergens, is the only diseasemodifying treatment for allergy. Current therapeutic allergy vaccines are still prepared from relatively poorly defined allergen extracts. However, with the availability of the structures of the most common allergen molecules, it has become possible to produce well-defined recombinant and synthetic allergy vaccines that allow specific targeting of the mechanisms of allergic disease. Here we provide a summary of the development and mechanisms of SIT, and then review new forms of therapeutic vaccines that are based on recombinant and synthetic molecules. Finally, we discuss possible allergen-specific strategies for prevention of allergic disease.

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Prevention of allergen‐specific IgE production and suppression of an established Th2‐type response by immunization with DNA encoding hypoallergenic allergen derivatives of Bet v 1, the major birch‐pollen allergen

Cited by 52 publications

References 25 publications

A Recombinant Hypoallergenic Parvalbumin Mutant for Immunotherapy of IgE-Mediated Fish Allergy

A Recombinant Hypoallergenic Parvalbumin Mutant for Immunotherapy of IgE-Mediated Fish Allergy

Is Genetic Vaccination against Allergy Possible?

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

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