title: Cofactor independent phosphoglycerate mutase of Brugia malayi induces 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 parasite Brugia malayi was 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 vivo immunological behaviour of protein was determined in immunized BALB/c mice followed by prophylactic analysis in BALB/c mice and Mastomys 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 in M. coucha. In vitro studies confirmed participation of anti-Bm-iPGM antibodies in killing of B. malayi infective larvae and microfilariae through ADCC mechanism. The present findings reveal potential immunoprotective nature of Bm-iPGM advocating its worth as an antifilarial vaccine candidate.
authors: Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, P.O. Box 173, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh 226031, India.
authors: Prashant K
authors: PK
authors: Singh
authors: Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, P.O. Box 173, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh 226031, India.
authors: Susheela
authors: S
authors: Kushwaha
authors: Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, P.O. Box 173, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh 226031, India.
authors: Ajay K
authors: AK
authors: Rana
authors: Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, P.O. Box 173, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh 226031, India.
authors: Shailja
authors: S
authors: Misra-Bhattacharya
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology; D017178:Brugia malayi / Q000201:enzymology / Q000276:immunology*; D005368:Filariasis / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D015801:Helminth Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007814:Larva / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010736:Phosphoglycerate Mutase / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D014612:Vaccines / Q000276:immunology
chemical_list: D000909:Antibodies, Helminth; D015801:Helminth Proteins; D014612:Vaccines; D010736:Phosphoglycerate Mutase