Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen Bet v 1.
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.
Vrtala
S
S
Department of Pathophysiology, Vienna General Hospital, University of Vienna Medical School, Waeringer Guertel 18-20, A-1090 Vienna, Austria
Hirtenlehner
K
K
Susani
M
M
Akdis
M
M
Kussebi
F
F
Akdis
C A
CA
Blaser
K
K
Hufnagl
P
P
Binder
B R
BR
Politou
A
A
Pastore
A
A
Vangelista
L
L
Sperr
W R
WR
Semper
H
H
Valent
P
P
Ebner
C
C
Kraft
D
D
Valenta
R
R
D000485:Allergens / Q000235:genetics / Q000276:immunology*; D052179:Antigens, Plant; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005818:Genetic Engineering; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D010940:Plant Proteins; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E