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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2013.tde-03062014-160754
Document
Author
Full name
Renan Antonialli
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Boscardin, Silvia Beatriz (President)
Barboza, Renato
Barbuto, Jose Alexandre Marzagao
Title in Portuguese
Efeito de ligantes de receptores semelhantes a Toll na resposta imune induzidas por antígenos direcionados ao DEC205 e DCIR2.
Keywords in Portuguese
Plasmodium
Anticorpos monoclonais
Antígenos
Linfócitos
Vacinas
Abstract in Portuguese
As células dendríticas (DCs) expressam receptores que reconhecem padrões moleculares associados a patógenos (PAMPs), sendo capazes de capturar, processar e apresentar antígenos para os linfócitos. O contato com PAMPs induz a maturação das DCs e, consequentemente, a ativação dos linfócitos. Nossa estratégia para desenvolver vacinas é empregar anticorpos monoclonais contra os receptores endocíticos DEC205 e DCIR2, presentes nas subpopulações de DCs, em fusão com o antígeno de interesse. E estimular a maturação delas utilizando os adjuvantes poly I:C, CpG ODN 1826 e flagelina de S. Typhimurium . Imunizamos camundongos selvagens ou knockouts para os receptores TLR 3, 5 e 9 com adjuvantes e anticorpos quiméricos anti-DEC205, anti-DCIR2 ou isotipo controle (Iso) fundidos a proteína MSP119 de Plasmodium vivax. Avaliamos as repostas humoral e celular no grupos imunizados. Os resultados indicam que, seja qual for o adjuvante usado, a maioria dos parâmetros analisados aponta para a superioridade do direcionamento do antígeno para o receptor DEC205.
Title in English
Effect of Toll-like receptors ligands in the immune response induced by antigens targeted to DEC205 and DCIR2.
Keywords in English
Plasmodium
Antigens
Lymphocytes
Monoclonal antibodies
Vaccines
Abstract in English
Dendritic cells (DCs) express receptors that recognize pathogen-associated molecular patterns (PAMPs), and are able to capture, process and present antigens to lymphocytes. In recent years, a immunization strategy that directs antigens to DCs in vivo has been developing. This consists in the use of monoclonal antibodies fused with the antigen of interest. However, effective immune activation occurs mainly when the chimeric antibodies anti-DEC or anti-DCIR2 are administered in the presence of a DC maturation stimulus. We immunized wild type and knockout mice for TLR3, 5 and 9 with adjuvants (poly I:C, CpG ODN 1826 and flagellin from S. typhimurium) and chimeric anti-DEC205, anti-DCIR2 or isotype control fused to the Plasmodium vivax MSP119 protein. After the administration of two doses, we evaluated the humoral and cellular immune responses in the different groups. Our results indicate that, irrespectively of the adjuvant, the majority of parameters analyzed points out to the superiority of antigen targeting to the DEC205 receptor.
 
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Publishing Date
2014-06-05
 
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