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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2019.tde-23122021-120633
Document
Author
Full name
Marcelo Valdemir de Araujo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Taborda, Carlos Pelleschi (President)
Almeida, Sandro Rogerio de
Correa, Benedito
Santos, André Luis Souza dos
Title in Portuguese
Incorporação do peptídeo sintético (P10) de P. brasiliensis com lípideo catiônico e sua ação sobre a resposta em camundongos C57Bl/6 e BALB/c infectados com Paracoccidioides brasiliensis.
Keywords in Portuguese
Adjuvante
DDA/TDB
Micose pulmonar
Paracoccidioidomicose
Vacina fúngica
Abstract in Portuguese
A paracoccidioidomicose (PCM) é uma micose sistêmica granulomatosa cujo agente etiológico é o fungo termodimórfico Paracoccidioides spp.. A doença é amplamente distribuída pela América Latina com maior número de casos no Brasil, Argentina, Venezuela e Colômbia. Atinge principalmente trabalhadores rurais trazendo importantes repercussões econômico-produtivas dos indivíduos acometidos. A PCM apresenta três quadros clínicos: forma assintomática, aguda ou subaguda (tipo juvenil), e crônica (tipo adulto). O antígeno imunodominante de Paracoccidioides brasiliensis é a gp43, onde um trecho específico de 15 aminoácidos, designado como P10, é reconhecido pelos linfócitos T desencadeando uma resposta pró- inflamatória contra a infecção fúngica. O presente estudo, avaliou a utilização do adjuvante a base de lipídeo catiônico (DDA) com o peptídeo sintético P10. Os resultados mostraram que o adjuvante sozinho tem pouca estabilidade e baixa imunogenicidade, a adição da carboximetilcelulose (CMC) aumentou a estabilidade do complexo DDA/CMC/P10, porém sem indução de resposta imune protetora devido as baixas concentrações dos componentes. A incorporação da trealose dibehenato (TDB) aumentou as características físico-químicas e imunogênicas do DDA e do peptídeo P10 refletindo na diminuição da carga fúngica nos pulmões dos camundongos C57Bl/6 infectados com Pb18, induzindo robusta resposta imune celular com altos níveis de citocinas pró inflamatórias Th1/Th17. O estudo demonstrou também que a utilização do glicolipídeo.
Title in English
Incorporation of the synthetic peptide (P10) from Paracoccidioides brasiliensis in cationic lipid (DDA) and its action on the immune response in C57Bl/6 and BALB/c mice infected with P. brasiliensis.
Keywords in English
Adjuvant
DDA/TDB
Fungal vaccine
Paracoccidioidomycosis
Pulmonary mycosis
Abstract in English
Paracoccidioidomycosis (PCM) is a granulomatous systemic mycosis whose etiologic agent is thermal dimorphic fungus Paracoccidoides spp., the disease is widely distributed in Latin America with the highest number of cases in Brazil, Argentina, Venezuela, and Colombia. It reaches mainly rural workers bringing important economic-productive repercussions of affected individuals. PCM presents three clinical manifestations: asymptomatic, acute or subacute (juvenile type), and chronic (adult type). The immunodominant antigen of Paracoccidioides brasiliensis is gp43, a glycoprotein of 416 amino acids, where a specific stretch of 15 amino acids, designated as P10, is recognized by T lymphocytes triggering a pro-inflammatory response against the fungal infection. Previous studies have shown that immunization with P10 associated with some adjuvants decreases fungal load in the lungs of mice and increases levels of cytokines in homogenate pulmonary. The present study evaluated the use of adjuvant based on cationic lipid (DDA) with synthetic peptide P10. The results showed that adjuvant alone has not stability even in the presence of carboxymethylcellulose (CMC) which led to greater stability of DDA/CMC/P10 complex but without immunogenicity. The incorporation of dibehenate trehalose (TDB) increased the stability and immunogenic characteristics of DDA and P10 peptide by decreasing the fungal load of lungs of C57Bl/6 mice infected with Pb18, inducing a robust cellular immune response with high levels of Th1/Th17 proinflammatory cytokines.
 
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Publishing Date
2022-01-13
 
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