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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2011.tde-13022012-080631
Document
Author
Full name
Catarina Joelma Magalhães Braga
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Ferreira, Luis Carlos de Souza (President)
Ho, Paulo Lee
Piazza, Roxane Maria Fontes
Rodrigues, Elaine Guadelupe
Sato, Maria Notomi
Title in Portuguese
Pesquisa de novos adjuvantes para vacinas terapêuticas.
Keywords in Portuguese
Adjuvantes imunológicos
HIV
Linfócitos
Neoplasias
Vacinas
Abstract in Portuguese
A busca por adjuvantes capazes de estimular eficiente resposta imunológica celular representa uma importante contribuição para a pesquisa de vacinas. No presente trabalho avaliamos o potencial adjuvante de flagelinas de Salmonella para a ativação de linfócitos T, com ênfase na ativação de linfócitos T CD8+, em animais imunizados com diferentes estratégias vacinais, desde vacinas baseadas em linhagens atenuadas de Salmonella; vacinas acelulares que empregaram flagelinas purificadas co-administradas, ou em fusão, a antígenos alvo e, ainda, vacinas de DNA. Nossos resultados demonstram que a utilização de flagelina na forma de vacina de DNA induziu maior proteção terapêutica que a mesma formulação utilizada na forma de vacinas de subunidades, sugerindo que os efeitos adjuvantes da flagelina para ativação de CTLs não estão relacionados apenas a ligação ao TLR5. Os resultados apresentados na presente tese contribuem para a compreensão dos mecanismos de adjuvanticidade da flagelina de Salmonella, particularmente no contexto da ativação de células T.
Title in English
Development of new adjuvants for therapeutic vaccine.
Keywords in English
HIV
Immune adjuvants
Lymphocytes
Neoplasms
Vaccines
Abstract in English
The search for adjuvants that are able to stimulate an efficient cellular immune response represents an important contribution in vaccine development. In this study, we evaluated the potential of Salmonella flagellin as adjuvant for activation of T lymphocytes, with emphasis on the activation of CD8+ T cells, on the mice immunized with different approaches such as vaccines based on attenuated Salmonella strains; acellular vaccines with purified flagellin co-administered or genetically fusioned to the target antigen; or even DNA vaccines. Our results demonstrate that the use of flagellin in the form of DNA vaccines induced greater therapeutic protection than the same formulation used in the form of subunit vaccines, suggesting that the adjuvant effects of flagellin to the activation of CTLs are related not only to link to TLR5. The results presented in this work contribute significantly to the understanding of the mechanisms of flagellin adjuvanticity, particularly in the context of activation of responses mediated by T cells.
 
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Publishing Date
2012-03-15
 
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