Banca de DEFESA: AYRTON BRENO PIMENTA LISBOA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : AYRTON BRENO PIMENTA LISBOA
DATA : 27/08/2019
HORA: 09:30
LOCAL: Auditório 4º Andar,Instituto de Ciências da Saúde - UFBA
TÍTULO:

Structural Bioinformatics of House Dust Mite Proteins: Implications for the Production of Hypoallergenic Vaccines and Improved Diagnostics

PALAVRAS-CHAVES:
PÁGINAS: 100
GRANDE ÁREA: Outra
ÁREA: Tecnologia e Inovação
RESUMO:

Allergies are type I immune hypersensitivity reactions, triggered by the binding of specific allergens to IgE antibodies that affect more than 25% of the world's population. In patients with allergic diseases and/or reactions, most of them are typically allergic to dust mites. Respiratory diseases caused by mites are treated with symptomatic medication or allergen-specific immunotherapy (AIT), based on purified extracts of mite bodies, feces or both. However, the use of crude extracts in immunotherapy containing various uncharacterized allergens can lead to severe side effects and patient sensitization to the allergens present in the mixture. Bioinformatics and genetic engineering tools enable changes in the structure of complete allergens as well as in B or T cell epitope regions as a strategy for formulating hypoallergenic immunotherapies. The objective of this study is the creation and implementation of a structural bioinformatics analysis pipeline that allows the design of hypoallergenic mite proteins, maintaining their immunogenic capacities, for future applications in immunotherapies. Structural bioinformatics methodologies were used to analyze the structures of the Der p 1 and Der p 21 allergens of the Dermatophagoides pteronyssinus mite. Immunoinformatics tools were used to scan possible mutations in key epitopes for IgE binding. After effective implementation of the structural analysis pipeline, destabilizing mutations of the major epitope regions were selected according to the variation of Gibbs free energy (kcal/mol) relative to wild-type proteins. Four mutant versions of Der p 21 protein (mutations: E77G, D82P, E87S, and K110G) were designed and modeled, as well as three mutants of Der p 1 (mutations: D189A, R147D, D189A). Der p 21 mutant protein D82P is currently undergoing experimental validation and has shown promising hypoallergenization results. The results presented here will potentially contribute to the development of safer recombinant vaccines for dust mite allergies in the future.

MEMBROS DA BANCA:
Interno - 1621863 - ERIC ROBERTO GUIMARAES ROCHA AGUIAR
Presidente - 1818609 - LUIS GUSTAVO CARVALHO PACHECO
Externo ao Programa - 2415395 - THIAGO LUIZ DE PAULA CASTRO