Cofactor Independent Phosphoglycerate Mutase ofBrugia malayiInduces a Mixed Th1/Th2 Type Immune Response and Inhibits Larval Development in the Host

Abstract

Lymphatic filariasis is a major debilitating disease, endemic in 72 countries putting more than 1.39 billion people at risk and 120 million are already infected. Despite the significant progress in chemotherapeutic advancements, there is still need for other measures like development of an effective vaccine or discovery of novel drug targets. In this study, structural and immunological characterization of independent phosphoglycerate mutase of filarial parasiteBrugia malayiwas carried out. Protein was found to be expressed in all major parasite life stages and as an excretory secretory product of adult parasites. Bm-iPGM also reacted to all the categories of human bancroftian patient’s sera including endemic normals.In vivoimmunological behaviour of protein was determined in immunized BALB/c mice followed by prophylactic analysis in BALB/c mice andMastomys coucha. Immunization with Bm-iPGM led to generation of a mixed Th1/Th2 type immune response offering 58.2% protection against larval challenge in BALB/c and 65–68% protection inM. coucha.In vitrostudies confirmed participation of anti-Bm-iPGM antibodies in killing ofB. malayiinfective larvae and microfilariae through ADCC mechanism. The present findings reveal potential immunoprotective nature of Bm-iPGM advocating its worth as an antifilarial vaccine candidate.