Potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos
Toxoplasmosis is a zoonotic worldwide disease caused by the protozoan Toxoplasma gondii (T. gondii), which can infect several warm-blooded animals, including humans. The most severe symptoms are usually observed in immunosupressed patients and could even be fatal. Due to the great biological diversi...
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Toxoplasmose Imunoinformática Epítopos Vacinas Imunodiagnóstico CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
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Toxoplasmose Imunoinformática Epítopos Vacinas Imunodiagnóstico CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA Moura, Andrew Douglas Potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos |
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Toxoplasmosis is a zoonotic worldwide disease caused by the protozoan Toxoplasma gondii (T. gondii), which can infect several warm-blooded animals, including humans. The most severe symptoms are usually observed in immunosupressed patients and could even be fatal. Due to the great biological diversity of non-clonal T. gondii isolates circulating in the southern hemisphere of the terrestrial globe, serious complications such as encephalitis, myocarditis and ocular damage can also be observed in immunocompetent individuals. Recently, a study revealed that T. gondii is also associated to the delineation of neurodegenerative diseases and a few types of cancers. Advances in immunoinformatics have been contributing with strategies to improve research on immunodominant epitopes contained in proteins from microorganisms, which can be recognized by host B and T cells. The study aims were to screen, analyze and select B and T cell epitopes contained in the Toxoplasma gondii AMA1, GRA7 and SAG1 proteins, as well as to construct chimeric peptides formed by the junction of B and T cell epitopes, and to analyze their immunogenic potential in silico and in vitro approaches. Four chimeric peptides were constructed, which showed binding affinities with murine and human MHC molecules in silico analyzes. A multi-antigenic epitopes chimera (TgAGS / BsT) was constructed from Toxoplasma gondii AMA1, GRA7 and SAG1 proteins by in silico analyzes, and expressed in recombinant system. The potential as diagnostic markers was confirmed by IgG recognition in serum-positive (n=10) for Toxoplasmosis by ELISA. Through antigenic stimuli in PBMC culture from immunocompetent serum-negative and serum-positive Toxoplasmosis persons, the expression of CD25 + in CD3 + cells was induced in the positive group of persons, with significance results (p<0.05), when compared to negative individuals. In addition, the production of IFN-y and IL-2 cytokines were found in supernatant cultures stimulated by the chimeric peptides. These findings open perspectives for the development of vaccines and diagnostic reagents for Toxoplasmosis through chimeric products formed by B-cell epitopes and T. |
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Salha, Daniella Regina Arantes Martins |
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Salha, Daniella Regina Arantes Martins Moura, Andrew Douglas |
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doctoralThesis |
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Moura, Andrew Douglas |
| author_sort |
Moura, Andrew Douglas |
| title |
Potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos |
| title_short |
Potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos |
| title_full |
Potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos |
| title_fullStr |
Potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos |
| title_full_unstemmed |
Potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos |
| title_sort |
potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos |
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Brasil |
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2018 |
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https://repositorio.ufrn.br/jspui/handle/123456789/25235 |
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AT mouraandrewdouglas potenciaisvacinasemarcadoresdediagnosticoparatoxoplasmosebaseadosempeptideosquimericos AT mouraandrewdouglas potencialvaccinesandadiagnosticmarkersfortoxoplasmosisbasedonchimericspeptides |
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ri-123456789-252352019-01-30T11:43:27Z Potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos Potencial vaccines anda diagnostic markers for toxoplasmosis based on chimerics peptides Moura, Andrew Douglas Salha, Daniella Regina Arantes Martins Romero, Oscar Bruña Silva Júnior, Arnóbio Antonio da Rodrigues Neto, João Firmino Bouillet, Leoneide Érica Maduro Schriefer, Nicolaus Albert Borges Toxoplasmose Imunoinformática Epítopos Vacinas Imunodiagnóstico CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA Toxoplasmosis is a zoonotic worldwide disease caused by the protozoan Toxoplasma gondii (T. gondii), which can infect several warm-blooded animals, including humans. The most severe symptoms are usually observed in immunosupressed patients and could even be fatal. Due to the great biological diversity of non-clonal T. gondii isolates circulating in the southern hemisphere of the terrestrial globe, serious complications such as encephalitis, myocarditis and ocular damage can also be observed in immunocompetent individuals. Recently, a study revealed that T. gondii is also associated to the delineation of neurodegenerative diseases and a few types of cancers. Advances in immunoinformatics have been contributing with strategies to improve research on immunodominant epitopes contained in proteins from microorganisms, which can be recognized by host B and T cells. The study aims were to screen, analyze and select B and T cell epitopes contained in the Toxoplasma gondii AMA1, GRA7 and SAG1 proteins, as well as to construct chimeric peptides formed by the junction of B and T cell epitopes, and to analyze their immunogenic potential in silico and in vitro approaches. Four chimeric peptides were constructed, which showed binding affinities with murine and human MHC molecules in silico analyzes. A multi-antigenic epitopes chimera (TgAGS / BsT) was constructed from Toxoplasma gondii AMA1, GRA7 and SAG1 proteins by in silico analyzes, and expressed in recombinant system. The potential as diagnostic markers was confirmed by IgG recognition in serum-positive (n=10) for Toxoplasmosis by ELISA. Through antigenic stimuli in PBMC culture from immunocompetent serum-negative and serum-positive Toxoplasmosis persons, the expression of CD25 + in CD3 + cells was induced in the positive group of persons, with significance results (p<0.05), when compared to negative individuals. In addition, the production of IFN-y and IL-2 cytokines were found in supernatant cultures stimulated by the chimeric peptides. These findings open perspectives for the development of vaccines and diagnostic reagents for Toxoplasmosis through chimeric products formed by B-cell epitopes and T. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) A Toxoplasmose é uma zoonose de distribuição mundial causada pelo protozoário Toxoplasma gondii (T. gondii), que pode infectar vários animais de sangue quente, incluindo humanos. Os sintomas mais graves geralmente são observados em indíviduos imussuprimidos, podendo ser fatal. Devido à grande diversidade biológica de isolados não-clonais de T. gondii circulantes no hemisfério sul do globo terrestre, complicações severas tais como encefalites, miocardites e danos oculares também podem ser observadas em indivíduos imunocompetentes. Recentemente, um estudo revelou que o T. gondii está associado no desencadeamento de doenças neurodegenerativas, e alguns tipos de câncer. Os avanços em imunoioinformática colaboram com estratégias para melhorar a busca e identificação de epítopos imunodominantes contidos em proteínas de microorganismos, os quais podem ser reconhecidos pelas células B e T hospedeira. O objetivo deste estudo foi mapear, analisar e selecionar epítopos de células B e T contidos nas proteínas AMA1, GRA7 e SAG1 de Toxoplasma gondii, assim como, construir peptídeos quiméricos formados pela junção de epítopos de células B e T, analisar seus potenciais imunogênico in silico e in vitro. Foram construídos quatro peptídeos quiméricos, os quais apresentaram afinidades de ligações com moléculas de MHC de murinos e humanos em análises in silico. Uma quimera multi-antigênica (TgAGS/BsT) composta por todos os epítopos dessas diferentes proteínas, foi construída, analisada in silico, e posteriormente obtida através da expressão em sistema recombinante. O pontencial como marcadores de diagnóstico foi confirmado através do reconhecimento de IgG em pacientes positivos para Toxoplasmose por ELISA (n=10). Através de estímulos antigênicos em cultura de PBMC de pacientes imunocompetentes IgG negativo e positivo para Toxoplasmose, foi induzida a expressão de CD25+ em células CD3+ no grupo de pacientes positivos com significância (p<0,05) quando comparados aos pacientes negativos. Além disso, foi verificada a produção de IFN- e IL-2 no sobrenadante de culturas estimuladas com os peptídeos quiméricos. Esses achados abrem perspectivas para o desenvolvimento de vacinas e reagentes de diagnóstico para Toxoplasmose através de produtos quiméricos formados por epítopos de células B e T. 2018-05-17T19:15:23Z 2018-05-17T19:15:23Z 2018-03-28 doctoralThesis MOURA, Andrew Douglas. Potenciais vacinas e marcadores de diagnóstico para toxoplasmose baseados em peptídeos quiméricos. 2018. 124f. Tese (Doutorado em Bioquímica) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2018. https://repositorio.ufrn.br/jspui/handle/123456789/25235 por Acesso Aberto application/pdf Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM BIOQUÍMICA |