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Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen Bet v 1.
Authors:S Vrtala  K Hirtenlehner  M Susani  M Akdis  F Kussebi  C A Akdis  K Blaser  P Hufnagl  B R Binder  A Politou  A Pastore  L Vangelista  W R Sperr  H Semper  P Valent  C Ebner  D Kraft  R Valenta
Affiliation:Department of Pathophysiology, Vienna General Hospital, University of Vienna Medical School, Waeringer Guertel 18-20, A-1090 Vienna, Austria
Abstract:An estimated 100 million individuals suffer from birch pollen allergy. Specific immunotherapy, the only curative allergy treatment, can cause life-threatening anaphylactic side effects. Here, we report the genetic engineering of a recombinant trimer consisting of three covalently linked copies of the major birch pollen allergen, Bet v 1. The trimer exhibited profoundly reduced allergenic activity but contained similar secondary structures such as Bet v 1 wild type, Bet v 1-specific B cell and T-cell epitopes, and induced Th1 cytokine release. As immunogen, rBet v 1 trimer induced IgG antibodies, which blocked patients' IgE binding to Bet v 1 and related allergens. Thus, rBet v 1 trimer represents a novel hypoallergenic vaccine prototype for treatment of one of the most frequent allergy forms.
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