PfRh5 Genetic and Antigenic in Tanzanian Asymptomatic Carriers: Field Evidence for Vaccine Efficacy Assessment

초록

Introduction : PfRl15 is one of the few indispensable ligands for Plasmodium falciparum erythrocyte invasion and is a leading candidate for blood-stage high-tansmission settings, genetic drift and heterogeneous immune responses may erode vaccine efficacy. We sought to evaluate PtRh5 genetic variation and antigenicity in asymptomatic carriers from Tanzania, providing field-based insights into vaccine potential. Material and Method : From December 2022 to July 2023, a cross-sectional survey was conducted i n Geita and Kigoma, two malaria-endemic regions of Tanzania. A total of 242 blood and serum samples were collected from asymptomatic individuals. Parasite DNA was sequenced to analyze pfrh5 diversity in l64 isolates. Recombinant PtRh5 protein mIcroarrays were used to assess antigenicity, and correlations with demographic and parasitological factors were examined. Results : The pfrh5gene showed overall conservation but carried novel non- synonymous mutations (D65H, H170N, l227M) with evidence of positive selection and recent population expansion. Antigenicity analysis revealed marked geographical differences: IgG prevalence was significantly higher in Geita (57.9%) compared to Kigoma (11.6%). Antibody response was positively correlated with age but showed no association with parasitemia or gender.Importantly, increased genetic polymorphism was linked with reduced- antigenicity, indicating possible challenges for cross-protective vaccine efficacy. Conclusions : This study offers field-based evidence that PtRh5 continues to be a promising vaccine target, while also highlighting the need to account for regional genetic variation and diverse immune responses. Incorporating data from endemic populations in!o PfRh5 vaccine development will be crucial to ensure broad、reliable, and lasting protection in malaria-endemic regions.