Biomedical subjects

S Vrtala

Publications and source records attributed to S Vrtala.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Mucosal tolerance induction with hypoallergenic molecules in a murine model of allergic asthma.

Type I allergy, frequently elicited by airborne allergens, has constantly increased within recent years. Birch pollen and its major allergen Bet v 1 represent a major source of type I allergens. By genetic engineering hypoallergenic Bet v 1 fragments were produced, which lost the IgE binding capacity but retained the T cell epitopes. We have established a murine model of aerosol sensitization to birch pollen and its major allergen Bet v 1, leading to type I allergic immune responses and airway hyperresponsiveness. In the present study we demonstrate that mucosal administration of recombinant Bet v 1 prior to sensitization led to allergen-specific suppression of B and T cell responses in vivo and in vitro, reduction of eosinophilic infiltration in the lungs and inhibition of airway hyperresponsiveness. Intranasal pretreatment with the nonanaphylactic fragments of Bet v 1 prevented allergic immune responses and airway inflammation to the same degree as the pretreatment with the complete molecule. We conclude from our studies that mucosal tolerance induction with hypoallergenic molecules could provide a safe and convenient treatment strategy against type I allergies.

Allergens↗

PubMedDate not supplied

Humoral immune responses to recombinant tree pollen allergens (Bet v I and Bet v II) in mice: construction of a live oral allergy vaccine.

Recombinant tree pollen allergens (recombinant Bet v I and recombinant birch profilin, Bet v II) were purified and used to immunize BALB/c and B6D2F1 mice with Al(OH)3 to elicit a specific IgE response. Serum from immunized mice was then used to detect immunoblotted natural tree pollen allergens. The onset of the humoral immune response was monitored using antimouse IgE, IgG1, IgG2a/b, IgG3 and IgA. In both strains, a specific and long-lasting IgE response could be elicited with both recombinant allergens. Mice immunized continuously with recombinant Bet v I + Al(OH)3 showed a significant decrease of specific IgE antibodies indicating that continuous application of allergens can reduce specific IgE responses. The possibility of inducing a different type of immune responses is indicated by the fact that mice fed with Bet v I expressed in apathogenic Salmonella strains showed a Th1 immune response to Bet v I accompanied by specific IgG2a/b without detectable IgG1 or IgE. Recombinant allergens can hence be used to decrease or even modulate specific IgE responses in vivo.

Adjuvants, Immunologic↗

PubMedDate not supplied

Division of the major birch pollen allergen, Bet v 1, into two non-anaphylactic fragments.

We have expressed in Escherichia coli two halves of the major birch pollen allergen, Bet v 1. Both fragments representing the complete 17-kD allergen were purified to homogeneity. In contrast to the complete recombinant, Bet v 1, the fragments had almost completely lost their IgE-binding capacity and exhibited a random coil structure as analyzed by circular dichroism. The ability of the recombinant fragments to trigger histamine release from allergic patients' basophils as well as their capacity to elicit skin reactions were also largely abolished. Both non-anaphylactic Bet v 1 fragments carried the majority of T cell epitopes and may therefore be considered as safe tools for immunotherapy of tree pollen and associated food allergy.

Allergens↗

PubMedDate not supplied

Genetically engineered and synthetic allergen derivatives: candidates for vaccination against type I allergy.

Type I allergy, a hypersensitivity disease affecting almost 20% of the population worldwide, is based on the IgE recognition of otherwise harmless antigens (i.e., allergens). Allergen-induced crosslink of effector cell-bound IgE antibodies leads to the release of biological mediators and thus to immediate disease symptoms (allergic rhinitis, conjunctivitis and asthma). Specific immunotherapy, the only causative treatment of Type I allergy, is based on the administration of increasing doses of allergens to allergic patients in order to yield allergen-specific non-responsiveness. Major disadvantages are 1. that current forms of allergen immunotherapy are performed with allergens difficult to standardize which cannot be matched to the patients reactivity profile and 2. that the administration of active allergen preparations can cause anaphylactic side effects. Through the application of molecular biological techniques many relevant environmental allergens have been produced as active recombinant proteins which allow component-resolved allergy diagnosis and thus represent the basis for patient-tailored forms of immunotherapy. Here we review molecular strategies which have been recently applied to generate genetically engineered and synthetic hypoallergenic allergen derivatives for patient-tailored and safe vaccination against Type I allergy.

Allergens↗