Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination.
BACKGROUND
Almost 100 million allergic patients are sensitized to the major birch pollen allergen, Bet v 1, a 17 kDa protein containing most of the IgE epitopes present in pollens of trees belonging to the Fagales order and plant-derived food.


OBJECTIVE
Our aim was to develop an approach for the rational design of B cell epitope-derived, non-allergenic peptide allergy vaccines.


METHODS
According to the three-dimensional (3-D) structure of birch pollen allergen, Bet v 1, six peptides comprising 25-32 preferably solvent-exposed amino acids were synthesized.


RESULTS
Because of lack of secondary structure, the peptides showed no allergenic activity in allergic patients. In a mouse model of birch pollen allergy, peptide vaccination induced Bet v 1-specific IgG and prevented IgE-mediated allergic sensitization to Bet v 1. The protective role of peptide-induced blocking antibodies is demonstrated by inhibition of allergic patients IgE binding to the allergen and by blocking of allergen-induced basophil degranulation.


CONCLUSIONS
Our results indicate the mechanistic importance of blocking antibodies for allergy vaccination and present a B cell epitope-based approach for the rational design of safe peptide allergy vaccines whenever the structure of the disease-eliciting allergen is known.
Department of Pathophysiology, Vienna General Hospital, Medical University of Vienna, Austria. rudolf.valenta@meduniwien.ac.at
M
M
Focke
B
B
Linhart
A
A
Hartl
U
U
Wiedermann
W R
WR
Sperr
P
P
Valent
J
J
Thalhamer
D
D
Kraft
R
R
Valenta
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D052179:Antigens, Plant; D001402:B-Lymphocytes / Q000276:immunology; D001491:Basophils / Q000276:immunology; D029662:Betula / Q000276:immunology*; D003888:Desensitization, Immunologic / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D017434:Protein Structure, Tertiary; D011817:Rabbits; D051381:Rats; D012882:Skin Tests / Q000379:methods; D014612:Vaccines / Q000276:immunology*
D000485:Allergens; D052179:Antigens, Plant; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides; D014612:Vaccines; D007073:Immunoglobulin E