Proteome-Wide Identification of Immunodominant Antigens of Wuchereria bancrofti for Vaccine Development Against Lymphatic Filariasis in Nigeria

📖 ABSTRACT/OVERVIEW

Despite decades of mass drug administration, lymphatic filariasis caused by Wuchereria bancrofti remains endemic in Nigeria, and the development of a prophylactic vaccine targeting macrofilaricidal or transmission-blocking endpoints is increasingly recognised as necessary for achieving elimination. This doctoral research performs proteome-wide identification of immunodominant W. bancrofti antigens using sera from naturally immune Nigerian adults and bioinformatic prioritisation for vaccine candidate selection. Adult W. bancrofti microfilariae and L3 infective larvae were obtained from infected Culex quinquefasciatus maintained under laboratory conditions at the Nigerian Institute for Medical Research Lagos. Parasite proteins were separated by two-dimensional gel electrophoresis and subjected to immunoblotting with pools of sera from putatively immune microfilaria-negative individuals residing in endemic communities in Ogun and Lagos States. Immunoreactive spots were excised and identified by LC-MS/MS. A complementary in silico immunoinformatics pipeline predicted MHC class I and II T cell epitopes and B cell epitopes from the top-ranked immunodominant proteins. Three lead vaccine candidates were selected based on antigenicity, surface accessibility, conservation across W. bancrofti strains, and druggability. Recombinant proteins were expressed in a Pichia pastoris system and used to immunise BALB/c mice, with larval challenge experiments assessing protective efficacy. Evidence from 2020 to 2024 identifies W. bancrofti abundant larval transcript proteins and venom allergen homologs as priority vaccine targets showing protective immunity associations. This study produces a Nigerian isolate-grounded vaccine development pipeline with direct translational potential. Keywords: Wuchereria bancrofti, immunodominant antigens, vaccine development, proteomics, lymphatic filariasis.

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Departments# Parasitology