In Search of a Vaccine for Mouse Allergy: Significant Reduction of Mus m 1 Allergenicity by Structure-Guided Single-Point Mutations

Mostrar registro simples Ferrari, Elena Breda, Daniela Longhi, Renato Vangelista, Luca Nakaie, Clovis Ryuichi [UNIFESP] Elviri, Lisa Casali, Emanuela Pertinhez, Thelma A. Spisni, Alberto Burastero, Samuele E. 2016-01-24T14:17:38Z 2016-01-24T14:17:38Z 2012-01-01
dc.identifier.citation International Archives of Allergy and Immunology. Basel: Karger, v. 157, n. 3, p. 226-237, 2012.
dc.identifier.issn 1018-2438
dc.description.abstract Background: Mouse urinary proteins are relevant allergens from mice urine. We used the recombinant protein Mus m 1 as an allergen model to identify if, by altering Mus m 1 architecture via single-point mutations, we could effectively modify its allergenicity. Methods: Based on structural considerations, we synthesized two single-point mutants, Mus m 1-Y120A and Mus m 1-Y120F, which were expected to harbor large structural alterations. Circular dichroism and fluorescence analysis showed significant conformational rearrangements of the aromatic side chains in the internal cavity of Mus m 1-Y120A when compared to Mus m 1-Y120F and Mus m 1. Evaluation of the allergenic potential of the recombinant molecules was performed in vitro with both immunochemical approaches and assays based on the measurement of basophil degranulation. Moreover, to assess the integrity of the T cell epitopes and as an in vitro measure of immunogenicity, we tested the reactivity of T lymphocytes from subjects allergic to mouse urine against proteins and synthetic peptides encompassing the immunodominant linear epitope containing the mutation. Results: We found that the selected point mutation was able to modulate the protein allergenicity, and to severely impair the recognition of Mus m 1 by IgE, while T cell reactivity was fully maintained. Conclusions: in silico predicted, minimum selected structural modifications allowed to design one protein with reduced allergenicity and preserved immunogenicity. Structurally guided mutations can direct the design of proteins with reduced allergenicity which can be used as vaccines for a safer and more effective immunotherapy of allergic disorders. Copyright (C) 2011 S. Karger AG, Basel en
dc.format.extent 226-237
dc.language.iso eng
dc.publisher Karger
dc.relation.ispartof International Archives of Allergy and Immunology
dc.rights Acesso aberto
dc.subject Allergen mutants en
dc.subject Allergenicity en
dc.subject Allergens en
dc.subject Allergoid en
dc.subject Lipocalin en
dc.subject Recombinant allergens en
dc.subject Recombinant hypoallergenic allergens en
dc.subject Basophil activation test en
dc.subject T cell epitopes en
dc.title In Search of a Vaccine for Mouse Allergy: Significant Reduction of Mus m 1 Allergenicity by Structure-Guided Single-Point Mutations en
dc.type Artigo
dc.contributor.institution Ist Sci San Raffaele
dc.contributor.institution Univ Parma
dc.contributor.institution CNR
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Ist Sci San Raffaele, IT-20132 Milan, Italy
dc.description.affiliation Univ Parma, Dept Expt Med, I-43100 Parma, Italy
dc.description.affiliation Univ Parma, Dept Gen & Inorgan Chem Analyt Chem & Phys Chem, I-43100 Parma, Italy
dc.description.affiliation CNR, Inst Chem & Mol Recognit, I-20133 Milan, Italy
dc.description.affiliation Universidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.identifier.doi 10.1159/000327551
dc.description.source Web of Science
dc.identifier.wos WOS:000300405800003

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