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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2017.tde-11052017-141914
Document
Author
Full name
Kelly Nazaré da Silva Amorim
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Boscardin, Silvia Beatriz (President)
Ho, Paulo Lee
Mauro, Eliana Faquim de Lima
Rodrigues, Elaine Guadelupe
Soares, Irene da Silva
Title in Portuguese
Direcionando a proteína MSP142 de Plasmodium vivax in vivo para o subtipo DEC205+CD8α+ de células dendríticas: análise das respostas imunes celular e humoral.
Keywords in Portuguese
Anticorpos monoclonais
Células dendríticas
DEC205
Malária
Abstract in Portuguese
Estudos conduzidos por vários grupos demonstraram que é possível direcionar antígenos para diferentes subtipos células de dendríticas (DCs) utilizando anticorpos monoclonais (mAbs). Neste trabalho, fusionamos o mAb αDEC205 a dois fragmentos de massa molecular aproximada de 42 e 19 kDa derivados da proteína 1 de superfície do merozoíto (MSP1) do Plasmodium vivax, um importante candidato para o desenvolvimento de uma vacina contra a malária. Para estudar a resposta induzida pelo direcionamento da proteína MSP142 e MSP119 para o subtipo de DCs DEC205+CD8α+, administramos duas doses dos mAbs na presença de poly (I:C), que é um agonista de TLR3 e MDA5. Nossos resultados indicam que o direcionamento da MSP142 para o subtipo de DCs DEC205+CD8α+ é capaz de induzir uma potente resposta celular contra o fragmento de 33 kDa e elevados títulos de anticorpos contra a porção de 19 kDa nas duas linhagens de camundongos.
Title in English
.Targeting the Plasmodium vivax MSP142 protein in vivo to the DEC205+CD8α+ dendritic cell subtype: analysis of the cellular and humoral immune responses.
Keywords in English
DEC205
Dendritic cells
Malaria
Monoclonal antibodies
Abstract in English
Studies conducted by several groups have shown that it is possible to target antigens to different subtypes dendritic cell (DC) using monoclonal antibodies (mAbs). Our group has been using a mAb that is able to direct the antigen to subtype of DCs DEC205+CD8α+ . In this work, we fused the αDEC205 mAb with a 42 and 19 kDa fragment derived from the Plasmodium vivax merozoite surface protein 1 (MSP1), a major candidate for the development of a malaria vaccine. In order to study the response induced by the MSP142 targeting to the DEC205+CD8α+ DC subtype, we administered two doses of the mAbs in the presence of poly (I: C), a TLR3 and MDA5 agonist. Our results indicate that MSP142 targeting to the DEC205+CD8α+ DC subtype is able to induce strong cellular response against the 33 kDa fragment, and high antibody titers against the 19 kDa portion in two strains of mice.
 
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Publishing Date
2017-05-29
 
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