PMU-Autor/inn/en
Hartl Arnulf JosefAbstract
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.
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.
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.
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.
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.
Useful keywords (using NLM MeSH Indexing)
Allergens/administration*
dosage*
Allergens/genetics
Allergens/immunology*
Allergens/toxicity
Animals
Antigens, Plant
Enzyme-Linked Immunosorbent Assay/methods
Female
Genetic Engineering
Hypersensitivity/immunology
Hypersensitivity/prevention*
control*
Immunoglobulin E/blood
Immunoglobulin G/blood
Immunotherapy/methods*
Male
Mice
Mice, Inbred BALB C
Plant Proteins/genetics
Plant Proteins/immunology*
Vaccines, Synthetic/administration*
dosage
Vaccines, Synthetic/genetics
Vaccines, Synthetic/toxicity
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genetic engineering