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Department of Pathophysiology, Vienna General Hospital, University of Vienna, Vienna, Austria; and
Swiss Institute of Allergy and Asthma Research, Davos, Switzerland
Allergen-specific immunotherapy represents one of the few curative
approaches toward type I allergy. Up to 25% of allergic patients are
sensitized against the major birch pollen allergen, Bet v 1. By genetic
engineering we produced two recombinant (r) Bet v 1 fragments
comprising aa 1–74 and aa 75–160 of Bet v 1, which, due to a loss of
their native-like fold, failed to bind IgE Abs and had reduced
allergenic activity. Here we show that both fragments covering the full
Bet v 1 sequence induced human lymphoproliferative responses similar to
rBet v 1 wild type. The C-terminal rBet v 1 fragment induced higher
lymphoproliferative responses than the N-terminal fragment and
represented a Th1-stimulating segment with high IFN-
production,
whereas the N-terminal fragment induced higher IL-4, IL-5, and IL-13
secretion. Immunization of mice and rabbits with rBet v 1 fragments
induced IgG Abs, which cross-reacted with complete Bet v 1 and Bet v
1-related plant allergens and strongly inhibited the IgE binding of
allergic patients to these allergens. Thus, our results demonstrate
that hypoallergenic T cell epitope-containing rBet v 1 fragments,
despite lacking IgE epitopes, can induce Abs in vivo that prevent the
IgE binding of allergic patients to the wild-type allergen. The overall
demonstration of the immunogenic features of the hypoallergenic rBet v
1 fragments will now enable clinical studies for safer and more
efficient specific immunotherapy.
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