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

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dc.contributor.authorFerrari, Elena
dc.contributor.authorBreda, Daniela
dc.contributor.authorLonghi, Renato
dc.contributor.authorVangelista, Luca
dc.contributor.authorNakaie, Clovis Ryuichi [UNIFESP]
dc.contributor.authorElviri, Lisa
dc.contributor.authorCasali, Emanuela
dc.contributor.authorPertinhez, Thelma A.
dc.contributor.authorSpisni, Alberto
dc.contributor.authorBurastero, Samuele E.
dc.contributor.institutionIst Sci San Raffaele
dc.contributor.institutionUniv Parma
dc.contributor.institutionCNR
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:17:38Z
dc.date.available2016-01-24T14:17:38Z
dc.date.issued2012-01-01
dc.description.abstractBackground: 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, Baselen
dc.description.affiliationIst Sci San Raffaele, IT-20132 Milan, Italy
dc.description.affiliationUniv Parma, Dept Expt Med, I-43100 Parma, Italy
dc.description.affiliationUniv Parma, Dept Gen & Inorgan Chem Analyt Chem & Phys Chem, I-43100 Parma, Italy
dc.description.affiliationCNR, Inst Chem & Mol Recognit, I-20133 Milan, Italy
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent226-237
dc.identifierhttp://dx.doi.org/10.1159/000327551
dc.identifier.citationInternational Archives of Allergy and Immunology. Basel: Karger, v. 157, n. 3, p. 226-237, 2012.
dc.identifier.doi10.1159/000327551
dc.identifier.issn1018-2438
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34381
dc.identifier.wosWOS:000300405800003
dc.language.isoeng
dc.publisherKarger
dc.relation.ispartofInternational Archives of Allergy and Immunology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://www.karger.com/Services/RightsPermissions
dc.subjectAllergen mutantsen
dc.subjectAllergenicityen
dc.subjectAllergensen
dc.subjectAllergoiden
dc.subjectLipocalinen
dc.subjectRecombinant allergensen
dc.subjectRecombinant hypoallergenic allergensen
dc.subjectBasophil activation testen
dc.subjectT cell epitopesen
dc.titleIn Search of a Vaccine for Mouse Allergy: Significant Reduction of Mus m 1 Allergenicity by Structure-Guided Single-Point Mutationsen
dc.typeinfo:eu-repo/semantics/article
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