BACKGROUND: The major allergens of trees belonging to the Fagales order are collectively known as the Bet v 1 family. Members of the Fagales order have distinct geographic distribution, and it is expected that depending on the exposure pattern of the individual, inclusion of other Bet v 1 family members might increase the efficacy of the treatment. OBJECTIVE: We aimed to generate molecules that are suitable for specific immunotherapy not only against birch pollen allergy but also against allergies caused by other cross-reactive tree pollens. METHODS: Fourteen genes of the Bet v 1 family were randomly recombined in vitro by means of DNA shuffling. This library of chimeric proteins was screened for molecules displaying low capacity to induce release of inflammatory mediators but with T-cell immunogenicity higher than that of the parental allergens. RESULTS: Two chimeric proteins were selected from the library of shuffled clones displaying low allergenicity and high immunogenicity, as determined in in vitro assays using human and animal cells and antibodies, as well as in vivo in animal models of allergy. CONCLUSION: Our results show that it is possible to randomly recombine in vitro T- and B-cell epitopes of a family of related allergens and to select chimeric proteins that perfectly match the criteria presently thought to be relevant for improving allergen-specific immunotherapy. CLINICAL IMPLICATIONS: The hypoallergenic chimeras described here recombine epitopes of the major Fagales pollen allergens and thus can efficiently substitute a mixture of extracts used for treating patients with tree pollen-induced spring pollinosis worldwide.
BACKGROUND: The major allergens of trees belonging to the Fagales order are collectively known as the Bet v 1 family. Members of the Fagales order have distinct geographic distribution, and it is expected that depending on the exposure pattern of the individual, inclusion of other Bet v 1 family members might increase the efficacy of the treatment. OBJECTIVE: We aimed to generate molecules that are suitable for specific immunotherapy not only against birch pollen allergy but also against allergies caused by other cross-reactive tree pollens. METHODS: Fourteen genes of the Bet v 1 family were randomly recombined in vitro by means of DNA shuffling. This library of chimeric proteins was screened for molecules displaying low capacity to induce release of inflammatory mediators but with T-cell immunogenicity higher than that of the parental allergens. RESULTS: Two chimeric proteins were selected from the library of shuffled clones displaying low allergenicity and high immunogenicity, as determined in in vitro assays using human and animal cells and antibodies, as well as in vivo in animal models of allergy. CONCLUSION: Our results show that it is possible to randomly recombine in vitro T- and B-cell epitopes of a family of related allergens and to select chimeric proteins that perfectly match the criteria presently thought to be relevant for improving allergen-specific immunotherapy. CLINICAL IMPLICATIONS: The hypoallergenic chimeras described here recombine epitopes of the major Fagales pollen allergens and thus can efficiently substitute a mixture of extracts used for treating patients with tree pollen-induced spring pollinosis worldwide.
Authors: Michael Wallner; Michael Hauser; Martin Himly; Nadja Zaborsky; Sonja Mutschlechner; Andrea Harrer; Claudia Asam; Ulrike Pichler; Ronald van Ree; Peter Briza; Josef Thalhamer; Barbara Bohle; Gernot Achatz; Fatima Ferreira Journal: J Allergy Clin Immunol Date: 2011-03-21 Impact factor: 10.793
Authors: Matthias Egger; Alexander Jürets; Michael Wallner; Peter Briza; Silke Ruzek; Stefan Hainzl; Ulrike Pichler; Claudia Kitzmüller; Barbara Bohle; Christian G Huber; Fátima Ferreira Journal: PLoS One Date: 2011-02-16 Impact factor: 3.240
Authors: C Gómez-Casado; M Garrido-Arandia; P Gamboa; N Blanca-López; G Canto; J Varela; J Cuesta-Herranz; L F Pacios; A Díaz-Perales; L Tordesillas Journal: Clin Dev Immunol Date: 2013-11-14