Vaccines for birch pollen allergy based on genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1.
BACKGROUND
We have recently engineered recombinant derivatives of the major birch pollen allergen Bet v 1 (rBet v 1 fragments and trimer) with strongly reduced allergenic activity.


OBJECTIVE
The aim of this study was the in vivo characterization of potential allergy vaccines based on Al(OH)3-adsorbed genetically modified rBet v 1 derivatives in mice.


METHODS
BALB/c mice were immunized either with courses of nine injections of increasing doses of Al(OH)3-adsorbed rBet v 1 wild-type, rBet v 1 fragments, rBet v 1 trimer or Al(OH)3 alone in weekly intervals or with three high-dose injections applied in intervals of 3 weeks. Humoral immune responses to rBet v 1 wild-type and homologous plant allergens were measured by ELISA and Western blotting, and the ability of mouse antibodies to inhibit the binding of allergic patients IgE to Bet v 1 was studied by ELISA competition experiments.


RESULTS
In both schemes, hypoallergenic rBet v 1 derivatives induced low IgE but high IgG1 responses against rBet v 1 wild-type. The IgG1 antibodies induced by genetically modified rBet v 1 derivatives cross-reacted with natural Bet v 1 and its homologues from alder (Aln g 1) as well as hazel (Cor a 1) and strongly inhibited the binding of birch pollen allergic patients' IgE to Bet v 1 wild-type.


CONCLUSIONS
Genetically modified hypoallergenic rBet v 1 derivatives induce blocking antibodies in vivo. Their safety and efficacy for the treatment of birch pollen and associated plant allergies can now be evaluated in clinical immunotherapy studies.
Mahler
V
V
Department of Dermatology, University of Erlangen, Germany.
Vrtala
S
S
Kuss
O
O
Diepgen
T L
TL
Suck
R
R
Cromwell
O
O
Fiebig
H
H
Hartl
A
A
Thalhamer
J
J
Schuler
G
G
Kraft
D
D
Valenta
R
R
D000485:Allergens / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D052179:Antigens, Plant; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005818:Genetic Engineering; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000633:toxicity
D000485:Allergens; D052179:Antigens, Plant; D007074:Immunoglobulin G; D010940:Plant Proteins; D014614:Vaccines, Synthetic; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E