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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-12032018-170059
Document
Author
Full name
Vanessa Cristina Nicolete
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Ferreira, Marcelo Urbano (President)
Boscardin, Silvia Beatriz
Lima Junior, Josué da Costa
Silveira, Eduardo Lani Volpe da
Title in Portuguese
Anticorpos contra a proteína de ligação em Duffy (PvDBP) e proteção contra a malária vivax na Amazônia rural brasileira.
Keywords in Portuguese
Anticorpos
mAb
Plasmodium
Proteção
PvDBP
Abstract in Portuguese
O ligante de merozoítos de Plasmodium vivax em DARC nos eritrócitos é PvDBPII. Aqui, nós testamos se anticorpos naturalmente adquiridos contra PvDBPII conferem proteção para malária vivax clínica em indivíduos da Amazônia. Para tanto, foram realizados ensaios multiplex com 466 indivíduos revelando uma alta proporção de respondedores. Porém, nenhuma associação entre níveis de anticorpos anti-PvDBPII e atraso para o próximo episódio de malária vivax foi encontrad a. Dessas amostras, 27,8% mostraram alta atividade inibitória e a presença desses anticorpos foi associada com atraso no próximo episódio de malária vivax. Para produzir um painel de anticorpos monoclonais (mAbs) anti-PvDBPII de indivíduos do Amazonas foi realizado um sorting de células B especificas de indivíduos com respostas inibitórias. Um desses mAbs competiu pelo mesmo sitio de ligação ou similar com anticorpos inibitórios naturalmente adquiridos. Em culturas P. vivax esse mAb foi capaz de reduzir a invasão de merozoítos em eritrócitos.
Title in English
Antibodies against Duffy Binding Protein (PvDBP) and protection against vivax malaria in brazilian rural Amazon.
Keywords in English
Antibodies
mAb
Plasmodium
Protection
PvDBP
Abstract in English
Merozoites of Plasmodium vivax has a critical parasite ligand (PvDBPII) that binds to DARC on erythrocytes. Here, we tested whether naturally acquired antibodies to PvDBPII conferred protection against clinical vivax malaria among rural Amazonians. We measured IgG antibodies from 466 individuals using a multiplex assay. A high proportion of samples tested had IgG antibodies to PvDBPII. However, found no association between high-level antibody response to PvDBPII and time to the next malaria episode. Of these samples, 27.8% displayed high blocking activity against PvDBP and these subjects had a statistically significant longer time to the next clinical P. vivax episode. To produce a panel of monoclonal antibodies (MoAbs) against PvDBPII from Amazon individuals, we sorted single PvDBPII-specific B-cell from subjects with BIAb responses. One of these MoAb generated recognizes PvDBPII and compete with naturally acquired antibodies from plasma samples to the same epitope recognized by MoAb. In short-term culture of Plasmodium vivax this Moab can reduced invasion.
 
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Publishing Date
2018-03-12
 
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