Modified beta-lactoglobulins for immunotherapy of milk allergy

摘要

The present invention is related to field of allergic (hypersensitivity) diseases and provides a method for producing modified allergenic polypeptides for use in immunotherapies. In the method of the invention, said allergenic polypeptides are modified so that they are not capable to form transient dimers. The invention also provides modified β-lactoglobulins for use in immunotherapy of milk allergy.

主权项

1. Method for preparing a hypoallergen candidate for immunotherapy comprising the steps of:
(a) altering monomer-monomer interface area of an allergenic polypeptide, wherein said monomer-monomer interface area is about or less than 850 Å2 and is related to the formation of transient dimers or oligomers in order to inactivate or reduce the polypeptide's natural ability to form transient dimers or oligomers, and wherein said allergenic polypeptide is selected from the group consisting of Bet v 2, Api m1, Der p 2, Api g 1, Che a 3, Api m 5, Phl p 6, Hev b 8, Gal d 4, Phl p 5, Gal d 3, Phl p 2, Mus m 1, Zea m 1, and Asp o 21; and (b) testing in vitro the altered polypeptide obtained from step (a) for ability to activate release of histamine or other mediators of an allergic reactions from human cells checking that a IgE antibody specific to said allergenic polypeptide still binds to the altered polypeptide obtained from step (a) to confirm that said allergenic polypeptide has a native-like structure and thus capability to prevent the crosslinking of the IgE-FcεRI complexes on a mast cell or basophile surface antibodies and immunogenic potential to develop protective IgG antibodies, wherein those altered polypeptides which do not activate histamine release or said other mediators or activate histamine release or said other mediators less than the parent polypeptide and which have said native-like structure are considered as hypoallergen candidates for immunotherapy.