Estudos biofísicos, estruturais e imunológicos de proteínas recombinantes correspondentes a antígenos de superfície de merozoítas de Plasmodium vivax / Studies biophysics, structural and immunological of recombinant proteins corresponding to merozoite surface proteins of Plasmodium vivax antigen

Diversas proteínas de superfície de merozoítas (MSPs) de Plasmodium têm sido consideradas a compor uma vacina contra a malária. Nos últimos anos estudamos diversos aspectos da reposta imune naturalmente adquirida contra proteínas recombinantes baseadas nas MSPs de P. vivax. Estes estudos demonstram que estas proteínas recombinantes mantêm suas funções imunológicas, podendo servir como base para a caracterização de suas estruturas tridimensionais. Com o objetivo de obter informações estruturais sobre as MSPs de P. vivax, 10 proteínas recombinantes, correspondentes à região C-terminal da MSP-1 (MSP119), e diferentes regiões da MSP-3α e MSP-3β foram expressas em Escherichia coli. Os dados estruturais da MSP119 foram obtidos por modelagem molecular com base nas coordenadas cristalográficas da MSP19 de P. cynomolgi. Por outro lado existem poucas informações estruturais sobre as proteínas da família MSP-3 de Plasmodium. A análise da estrutura primária dessas proteínas indica que elas apresentam um domínio central rico em alaninas que estão organizadas como motivos heptads...

Comparative recognition by human IgG antibodies of recombinant proteins representing three asexual erythrocytic stage vaccine candidates of Plasmodium vivax

In previous immuno-epidemiological studies of the naturally acquired antibody responses to merozoite surface protein-1 (MSP-1) of Plasmodium vivax, we had evidence that the responses to distinct erythrocytic stage antigens could be differentially regulated. The present study was designed to compare the antibody response to three asexual erythrocytic stage antigens vaccine candidates of P. vivax. Recombinant proteins representing the 19 kDa C-terminal region of MSP-1(PvMSP19), apical membrane antigen n-1 ectodomain (PvAMA-1), and the region II of duffy binding protein (PvDBP-RII) were compared in their ability to bind to IgG antibodies of serum samples collected from 220 individuals from the state of Pará, in the North of Brazil. During patent infection with P. vivax, the frequency of individuals with IgG antibodies to PvMSP1(19), PvAMA-1, and PvDBP-RII were 95, 72.7, and 44.5 percent respectively. Although the frequency of responders to PvDBP-RII was lower, this frequency increased in individuals following multiple malarial infections. Individually, the specific antibody levels did not decline significantly nine months after treatment, except to PvMSP1(19). Our results further confirm a complex regulation of the immune response to distinct blood stage antigens. The reason for that is presently unknown but it may contribute to the high risk of re-infection in individuals living in the endemic areas.