Perfil de resposta de anticorpos contra peptídeos lineares representando proteínas de fase exoeritrocítica (CelTOS e TRAP) e eritrocítica (CyRPA) de Plasmodium vivax durante a fase aguda e convalescente da infecção malárica

Abstract

Malaria is a global public health problem that mainly affects children and socially vulnerable people. In Brazil, the disease is endemic in the North region, with Plasmodium vivax being the predominant species with more than 80% of cases confirmed annually. The high number of clinical cases, the increasing resistance of parasites to the usual antimalarials, and the absence of an effective vaccine against malaria have contributed to the failure of programs to eliminate the disease around the world. There are only two licensed malaria vaccines, but both are aimed exclusively at infections by Plasmodium falciparum, the species that holds the great majority of studies on the disease, with only a few studies evaluating the complexity of the immune response in P. vivax, therefore, the understanding of the humoral response directed to different plasmodia proteins in regions of low endemicity is still necessary to guide the development of vaccines in these regions, especially in Brazil. Based on this, the present work aims to map the antibody response profile in individuals in the acute phase (D0) and convalescence (D30 and D180 after infection) of vivax malaria. To this end, synthetic peptides were used that represent linear portions of the proteins CelTOS and TRAP from the exoerythrocytic phase and CyRPA from the erythrocytic phase of P. vivax, all of them are potential vaccine candidates. The indirect ELISA with serum from patients from the Brazilian endemic region, infected or not, and from unexposed individuals was the method used to determine the positivity and magnitude of the reactivity indexes of IgM, IgG antibodies, and their subclasses. The reactivity index was also used to evaluate the response dynamics on days 0 and 30; 0 and 180; and 0, 30, and 180 post-infection for IgG and for correlation with clinical epidemiological parameters during the acute phase for IgG and IgM. The results obtained show that the studied population shows frequency and magnitude for all peptides and antibodies on different collection days. For IgM, a higher frequency of responders was associated with the erythrocytic phase peptide during the acute phase. For IgG, it was observed that a large portion of the studied population responds to proteins on different collection days, with emphasis on peptides from the exoerythrocytic phase where more than 40% respond at all points. During the analysis of IgG stability throughout the different points of the segment, it was observed that for all peptides, the antibodies remained stable up to 180 days after infection. Among the subclasses, IgG2, despite not being cytophilic, was the subclass that presented the most frequencies at the different collection points, while for the cytophilic ones, IgG3 was more prominent. Disease exposure factors did not show significant correlations with either IgG or IgM. We can conclude that the immunodominant epitopes presented here are naturally immunogenic in the studied population, presenting a frequency of responders and magnitude of reactivity index, both for total IgG and its subclasses, with the response being able to be maintained up to 180 days post-infection.