Vaccines for birch pollen allergy based on genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1
| Autor: | Thomas L. Diepgen, Helmut Fiebig, Oliver Kuss, Josef Thalhamer, Vera Mahler, Oliver Cromwell, Rudolf Valenta, Susanne Vrtala, Arnulf Josef Hartl, Gerold Schuler, Dietrich Kraft, Roland Suck |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Allergy Immunology Enzyme-Linked Immunosorbent Assay Immunoglobulin E medicine.disease_cause law.invention Mice Allergen Antigen law Hypersensitivity medicine Animals Immunology and Allergy Plant Proteins Mice Inbred BALB C Vaccines Synthetic biology Hypoallergenic Allergens Antigens Plant medicine.disease Genetically modified organism Immunoglobulin G biology.protein Recombinant DNA Female Immunotherapy Antibody Genetic Engineering |
| Zdroj: | Clinical Experimental Allergy. 34:115-122 |
| ISSN: | 1365-2222 0954-7894 |
| Popis: | Summary 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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