Immunogenetic Determinants of Susceptibility and Resistance to Lassa Fever in Predominantly Affected Communities in Ondo State

Lassa fever has a markedly variable clinical presentation, ranging from asymptomatic infection to fatal multiorgan failure, and growing evidence suggests that host immunogenetic variation is a primary determinant of disease outcome. In Ondo State, South West Nigeria, where Lassa fever incidence is highest nationally, population-level immunogenetic data are absent. This study characterises immunogenetic determinants of Lassa fever susceptibility and resistance in endemic communities in Ondo State. A case-control design will compare 150 hospitalised severe Lassa cases (PCR-confirmed), 150 seropositive asymptomatic individuals (ELISA-confirmed), and 150 seronegative healthy controls from endemic communities. Whole exome sequencing will identify rare coding variants in innate immunity genes. Genome-wide association study analysis of common variants will focus on HLA class I and II alleles, TLR, IFNAR, STAT1, TRIM5, and NPC1 (the cellular receptor for filoviruses, also relevant to mammarenaviruses). HLA typing by high-resolution next-generation sequencing will identify protective and susceptibility alleles. Functional validation will assess IFN-beta induction capacity by monocyte-derived dendritic cells from stratified genotype carriers. This study makes an original theoretical contribution by building the first immunogenetic risk model for Lassa fever in a West African endemic population, providing a framework applicable to vaccine target prioritisation and genetic risk stratification for prophylactic interventions in Ondo State communities. Keywords: Lassa fever, immunogenetics, susceptibility, HLA alleles, Ondo State