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Vaccines for birch pollen allergy based on genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1
Author(s) -
Mahler V.,
Vrtala S.,
Kuss O.,
Diepgen T. L.,
Suck R.,
Cromwell O.,
Fiebig H.,
Hartl A.,
Thalhamer J.,
Schuler G.,
Kraft D.,
Valenta R.
Publication year - 2004
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2004.01857.x
Subject(s) - hypoallergenic , allergen , immunoglobulin e , immunology , allergy , pollen , antibody , chemistry , medicine , biology , botany
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.

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