Epigenetic Regulation of Immune Evasion in Plasmodium falciparum Isolates from High and Low Transmission Zones in Nigeria: Implications for Vaccine Antigen Stability

Plasmodium falciparum exploits epigenetic mechanisms, including histone modifications and chromatin remodelling, to regulate antigenic variation and immune evasion, directly influencing the stability of vaccine target antigens across transmission intensities. This research investigates the epigenetic regulation of immune evasion genes in P. falciparum isolates from high-transmission North West Nigeria and low-transmission South West Nigeria, with the aim of characterising antigen expression variability that may undermine vaccine efficacy. Clinical isolates will be collected from 200 malaria patients across both zones. Chromatin immunoprecipitation sequencing targeting H3K9me3, H3K4me3, and HP1 binding at var, rifin, and stevor gene families will be performed using P. falciparum-adapted ChIP protocols. Nanopore sequencing will provide full-length var gene repertoire resolution and DNA methylation profiling. Proteomic analysis of surface antigen expression will correlate epigenetic states with phenotypic immune evasion. Cross-zone comparative analysis will identify transmission intensity-driven epigenetic adaptation. The research proposes a theoretical framework linking epidemiological transmission pressure to adaptive epigenetic parasite phenotypes. The original contribution includes the first comprehensive epigenomic characterisation of clinical Nigerian P. falciparum isolates and identification of transmission zone-specific epigenetic signatures relevant to antigen selection for next-generation malaria vaccines targeting Nigerian populations. Findings will contribute to rational vaccine antigen prioritisation aligned with Nigerian transmission ecology. Keywords: Plasmodium falciparum, epigenetics, antigenic variation, var genes, vaccine antigens