Monovalent fusion proteins of immunoglobulin E mimotopes are safe for therapy of type I allergy

被引:25
作者
Ganglberger, E
Sponer, B
Schöll, I
Wiedermann, U
Baumann, S
Hafner, C
Breiteneder, H
Suter, M
Boltz-Nitulescu, G
Scheiner, O
Jensen-Jarolim, E
机构
[1] Univ Vienna, Sch Med, Dept Pathophysiol, A-1090 Vienna, Austria
[2] Univ Zurich, Dept Virol, CH-8057 Zurich, Switzerland
关键词
Bet v 1; IgE epitope; ABP-fusion protein; blocking IgG;
D O I
10.1096/fj.00-0888fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
By screening phage display random peptide libraries with purified immunoglobulin E (IgE) from birch pollen-allergic patients, we previously defined peptides mimicking natural IgE epitopes (mimotopes) of the major birch pollen allergen Bet v 1. The present study aimed to define a monovalent carrier for the IgE mimotopes to induce protective antibodies directed to the IgE epitopes, suitable for mimotope-specific therapy. We expressed the selected mimotopes as fusion proteins together with streptococcal albumin binding protein (ABP). The fusion proteins were recognized specifically by anti-Bet v 1 human IgE, which demonstrated that the mimotopes fused to ABP resemble the natural IgE epitope. Bet v 1-specific IgG was induced by immunization of BALB/c mice with fusion proteins. These IgG antibodies could inhibit IgE binding to Bet v 1. Skin testing of Bet v 1 allergic mice showed that the ABP mimotope constructs did not elicit type I skin reactions, although they possess IgE binding structures. Our data suggest that IgE mimotopes are safe for epitope-specific immunotherapy of sensitized individuals, when presented in a monovalent form. Therefore, ABP-fused mimotopes are promising candidates for a new type of immunotherapy based on the precise induction of blocking antibodies.
引用
收藏
页码:2524 / +
页数:16
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