Immune Response Profiles to Plasmodium falciparum Blood Stage Antigens in Naturally Exposed Children in Benue State, North Central Nigeria

Naturally acquired immunity to Plasmodium falciparum blood stage antigens develops progressively with age and repeated exposure in malaria-endemic populations, providing protection against severe disease and serving as a template for malaria vaccine design. This study characterises immune response profiles to P. falciparum blood stage antigens in naturally exposed children in Benue State, North Central Nigeria. An analytical cross-sectional immunological study was conducted, recruiting 300 children aged 1 to 12 years from three communities in Makurdi, Agatu, and Apa Local Government Areas stratified by malaria exposure history. Peripheral blood was collected, and plasma was tested by ELISA for IgG antibody levels against merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and erythrocyte binding antigen 175 (EBA-175). Parasite density and anaemia status were assessed concurrently. Multivariate modelling examined the relationship between antibody levels, age, exposure intensity, and protection from high-density parasitaemia. Evidence from 2020 to 2024 demonstrates that multi-antigen IgG responses to MSP-1 and AMA-1 are the strongest correlates of naturally acquired protection against high-density parasitaemia in West African children. This study generates Benue State-specific immunological data with implications for identifying populations most likely to benefit from blood stage vaccine deployment. Findings will be submitted to a peer-reviewed immunology and parasitology journal. Keywords: Plasmodium falciparum, blood stage antigens, immune response, naturally exposed children, Benue State.