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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2015.tde-10122015-073215
Document
Author
Full name
Edione Cristina dos Reis
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Pontillo, Alessandra (President)
Lepique, Ana Paula
Nakaya, Helder Takashi Imoto
Title in Portuguese
Perfil genômico da resposta ao HIV-1 e implicações para a vacina terapêutica com células dendríticas contra o HIV-1.
Keywords in Portuguese
Células dendríticas
Ensaio clínico
HIV-1
Imunoterapia
Perfil genômico
Polimorfismos
Abstract in Portuguese
Esse trabalho objetivou avaliar o perfil genômico de pacientes HIV+ submetidos à imunoterapia com células dendríticas (DC). Os resultados obtidos mostraram que as DC utilizadas na imunoterapia podem ser diferentes em termos de perfil de expressão gênica entre os pacientes selecionados para o ensaio clínico e essas diferenças podem afetar a qualidade do produto administrado ao paciente. Nossos dados não correlacionaram diferenças na ativação das DC com esse perfil de expressão gênica distinto, possivelmente pelo número limitado de amostras disponíveis ou pela escassez de marcadores de ativação adequados. O único paciente que respondeu à imunoterapia mostrou, em leucócitos circulantes, um perfil de expressão específico e relacionado com um melhor controle da carga viral plasmática e com uma resposta imune de tipo Th1 quando comparado com os indivíduos que não responderam ao tratamento. A genotipagem revelou que esse paciente também carrega polimorfismos relacionados a menor progressão à AIDS o que também pode estar relacionado com a boa resposta à imunoterapia.
Title in English
Genomic profile of anti-HIV-1 response and outcome of dendritic cell-based therapeutic vaccine against HIV-1.
Keywords in English
Clinical trial
Dendritic cells
Genomic profile
HIV-1
Immunotherapy
Polymorphisms
Abstract in English
Aim of this project was the evaluation of genomic profile of HIV+ patients submitted to dendritic cell (DC)-based immunotherapy. Results showed that expression profile of DC used in immunotherapy could be different among patients selected for immunotherapy, and that those differences could affect the quality of final vaccine product, even if our data did not evidence significant difference in DC activation state with regard to expression profile, maybe due to limited size of available samples or to the lack of appropriate DC activation markers. The expression profile of peripheral blood leukocytes from the only good responder of immunotherapy trial was associated with better control of plasma viral load and a Th1 immune response compared to weak or transient responders. Genotyping analysis revealed that the good responder carries polymorphisms associated with a less progression toward AIDS, suggesting that also the genetic background could affect the response to immunotherapy.
 
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Publishing Date
2015-12-10
 
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