Porção variável de cadeia simples (scFv) anti-Glicosilfosfatidilinositol (GPI) de Plasmodium falciparum como alvo terapêutico para malária cerebral

Abstract

Malaria is an infectious disease caused by protozoa of the genus Plasmodium and is responsible for the deaths of thousands of people every year. Its complication to cerebral involvement primarily affects children and leads to the majority of deaths and sequelae associated with the disease. While there are treatment protocols primarily targeting the replication of the parasite, effective treatments for neurological manifestations are lacking, necessitating the exploration of new drug studies. In this study, our aim was to determine the potential therapeutic effect of a single-chain variable fragment (scFv) anti-Glycosylphosphatidylinositol (GPI) of Plasmodium in a preclinical assay. We utilized C57BL/6J mice infected with Plasmodium berghei-ANKA (PbA) and treated them with scFv anti-GPI or phosphate-buffered saline (PBS) on days 0, 3, and 6 post-infection. Uninfected controls were treated on the same days with scFv or PBS. Animals were assessed for morbidity and mortality, body weight, parasitemia, complete blood count, cytokines and histopathology. Our results indicate that treatment with scFv anti-GPI in PbA infected animals rescued 71.4% of the animals, promoted recovery from the initial weight loss caused by the infection, inhibited neurological signs of cerebral malaria (CM), as well as systemic disease signs, reduced parasitemia, improved blood parameters, induced pro-inflammatory cytokines, and decreased cerebral hemorrhages, demonstrating a significant therapeutic effect in experimental cerebral malaria pathology (ECM).