Towards an Original Immunogenomics-Based Framework for Next-Generation FMD Vaccine Development for West African Serotype Strains

This dissertation develops an original immunogenomics-based framework for rational next-generation foot-and-mouth disease vaccine design for the serotype strains predominating in West Africa, using Nigerian circulating strains as the foundational empirical basis. Current FMD vaccines provide inconsistent protection against Nigerian field strains due to antigenic mismatch, but a systematic immunogenomics approach to rational antigen redesign for West African conditions has not been attempted. The dissertation employs a four-phase design: comprehensive antigenic characterisation of FMDV serotype O, A, and SAT-2 isolates from Nigerian outbreaks using neutralisation titres, antigenic cartography, and structural epitope mapping; whole genome sequencing of 150 Nigerian isolates for phylogenomic and selection pressure analysis identifying immune-relevant VP1 sequence diversity; vaccinology experiments using guinea pig models comparing protection conferred by conventional and computationally redesigned antigen formulations; and immunogenomics analysis of protective immunity transcriptomics following vaccination and challenge. The study draws on samples from outbreaks across the North Central, North West, and South East geopolitical zones. The dissertation proposes the West African FMDV Antigen Design Protocol (WAFADP) as an original immunogenomics-based vaccinology framework. Primary findings reveal that the T-cell epitope landscape of Nigerian FMDV strains diverges significantly from vaccine strains at key positions in the VP1 immunodominant G-H loop, providing a structural basis for vaccine failure and a rational redesign target. Keywords: FMD vaccine, immunogenomics, antigenic cartography, West Africa, VP1.