doctoralThesis
Determinación del proteoma de la cepa VCG-1 de Plasmodium Vivax y caracterización de moléculas candidatas para su inclusión en el desarrollo de una vacuna
Fecha
2017Autor
Moreno Pérez, Darwin Andrés
Institución
Resumen
Identifying and characterising proteins which use Plasmodium merozoites to invade host cells represents an important strategy for developing a method for controlling these parasites. However, basic P. vivax research has been delayed due to difficulties in propagating it in vitro as the parasite prefers to invade reticulocytes; there is a low percentage of these in adult human peripheral blood (1%-2%) and they are difficult to obtain with high purity, in a sufficient amount and totally viable. Consequently, knowledge is scarce regarding the amount of molecules being expressed by P. vivax and which of them represent good candidates for inclusion in an effective vaccine. This study has been aimed at evaluating the proteome of a primate-adapted P. vivax strain; antigenic molecules able to bind to human reticulocytes have been characterised. Analysing the P. vivax VCG-1 strain proteome led to detecting 734 proteins, some of them essential in key steps for establishing merozoite invasion of target cells. Furthermore, 811 A. nancymaae primate erythrocyte components (vital Plasmodium hosts) were identified; 51 of them were integral membrane proteins, 7 described as Plasmodium receptors. The presence, transcription, expression and antigenicity of genes encoding three P. vivax molecules (PvARP, PvRBSA and PvGAMA) were identified. Particularly interesting was the finding that a higher percentage of PvRBSA and PvGAMA bound to reticulocytes abundantly expressing the CD71 receptor (CD71hi), thereby suggesting that these molecules could be participating in P. vivax merozoite preferential selection for human reticulocytes. This the first study in Colombia which has determined the protein composition of a primate-adapted P. vivax strain as well as A. nancymaae erythrocytes. More importantly, P. vivax molecules were characterised which appear to be suitable candidates for being evaluated as components of a vaccine against malaria caused by the parasite species.