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Master's Dissertation
DOI
10.11606/D.42.2007.tde-31102007-105256
Document
Author
Full name
Catarina Joelma Magalhães Braga
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Ferreira, Luis Carlos de Souza (President)
Martins, Elizabeth Angelica Leme
Taborda, Carlos Pelleschi
Title in Portuguese
Adordagem vacinal bivalente baseada na fusão genética de seqüência derivada da proteína circunsporozoíta (CS) de Plasmodium yoelii com a flagelina FliCd de Salmonella enterica
Keywords in Portuguese
Adjuvantes
Células T CD8+
Flagelina
Malária
Proteína circunsporzoíta
Vacinas terapêuticas
Abstract in Portuguese
A busca de adjuvantes que estimulem de forma eficiente à resposta imune celular representa uma importante contribuição para a pesquisa de vacinas. O principal objetivo deste trabalho foi a avaliação do efeito imunoestimulador de flagelinas expressas por linhagens de Salmonella sp., particularmente na ativação de respostas mediadas por células T CD8+, ao antígeno modelo ovalbumina. Em uma segunda etapa, foram investigados os efeitos adjuvantes da flagelina FliCd frente a um epítopo T CD8+, específico da proteína CS de P. yoelli. Animais foram imunizados com linhagens atenuadas de S. Dublin que expressam flagelinas geneticamente fusionadas ao epítopo CS ou com flagelina purificada co-administrada ou geneticamente fusionada ao antígeno alvo. A ativação de células T CD8+, foi monitorada por ELISPOT após estimulação com peptídeos específicos. Os resultados obtidos demonstram que a FliCd é capaz de modular o sistema imune, atuando particularmente na ativação de respostas mediadas por células T CD8+, sugerindo seu potencial para a composição de vacinas terapêuticas.
Title in English
Bivalent vaccines approaches based in genetic fusion of sequence derived of the circumsporozoíta (CS) protein de Plasmodium yoelii with FliCd flagellin of Salmonella enterica.
Keywords in English
Adjuvants
CD8+
Circumsporozoite protein
Flagellin
Malaria
T Cells
Therapeutic vaccines
Abstract in English
The search for adjuvants stimulating efficient cellular immune responses represents an important contribution in vaccine research. In the present work, we evaluated immunostimulatory effect of flagellins expressed by Salmonella sp. strains, particularly on activation of CD8+, T cells using ovalbumin as a model antigen. Secondly, we explored the adjuvant effect of the FliCd flagellin using an epitope from the CS protein of P. yoelli. Mice were immunized with S. Dublin strains that express flagellin genetically fused to CS epitope or purified flagellin co-administrated or genetically fused to the target antigen. The CD8+, T cells activation was monitored by ELISPOT after stimulation with specific peptides. Our results show that FliCd flagellin modulates the immune system, increasing CD8+, T cell activation, unveiling its potencial use in therapeutic vaccine approaches.
 
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Publishing Date
2007-11-06
 
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