Proteome-Wide Identification of Wuchereria bancrofti Excretory-Secretory Products as Diagnostic and Vaccine Candidate Antigens for Lymphatic Filariasis in Nigeria

📖 ABSTRACT/OVERVIEW

Excretory-secretory products released by Wuchereria bancrofti microfilariae and adult worms are the primary mediators of host-parasite immune interaction and represent a rich reservoir of potential diagnostic biomarkers and vaccine candidate antigens. This doctoral study conducted a proteome-wide characterisation of W. bancrofti excretory-secretory products from Nigerian field isolates as a platform for diagnostic and vaccine target discovery. Adult female worms recovered from experimentally infected Mongolian gerbils challenged with infective larvae derived from Nigerian Culex quinquefasciatus were cultured for 72 hours to collect excretory-secretory products. Two-dimensional gel electrophoresis coupled with LC-MS/MS identified 247 unique proteins. Bioinformatic prioritisation using signal peptide prediction, surface topology analysis, host immunoreactivity screening, and human ortholog selectivity filters shortlisted 18 candidate proteins. The top six candidates were recombinantly expressed in E. coli and evaluated for diagnostic performance using serum panels from 200 confirmed lymphatic filariasis patients and 200 endemic controls from Ogun State. Three antigens demonstrated sensitivity above 85 percent and specificity above 90 percent, outperforming the current filariasis test strip in antigen-negative amicrofilaraemic patients. Protective immunisation potential was preliminarily assessed in gerbil models, with two candidates inducing significant larval killing. This study provides a foundational target pipeline for next-generation lymphatic filariasis diagnostics and vaccines relevant to Nigerian W. bancrofti strains. Keywords: Wuchereria bancrofti, excretory-secretory products, proteomics, diagnostic antigens, vaccine candidates.

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