Testing the Efficacy of Fh15, a Recombinant Fatty Acid Binding Protein from Fasciola hepatica, as a Novel Anti-Inflammatory Biotherapeutic in an Acute Gram-Negative Non-Human Primate Sepsis Model

Abstract

Fasciola hepatica is known as a master of immunomodulation. Proteomic analyses have shown that Excretory/Secretory Products (ESP) have the capacity to evade the immune system to establish chronic infections. Fatty Acid Binding Proteins are a minor part of these ESP. Members of this family of proteins, such as Fh12 and Fh15, have shown to control the cytokine storm caused by the Lipopolysaccharide of Gram-negative bacteria. In this project, we determined the efficacy of Fh15 in a Non-Human Primate model, using Rhesus macaques. Results demonstrate that Fh15 is able to decrease bacteremia, endotoxemia, and hallmarks of sepsis, such as C-reactive protein and Procalcitonin. Furthermore, flow cytometry analyses demonstrated that Fh15 rescues the disappearance of immune effector cells on the blood. Moreover, Fh15 may induce the formation of METosis as the mechanism of action to decrease bacteremia and endotoxemia.