Profiling The Immune Response To The Duffy Binding-Like 5 (Dbl5) Domain Of Var2Csa In Pregnancy-Associated Malaria Among Women In Northern Ghana

BackgroundPregnancy-associated malaria (PAM), caused by Plasmodium falciparum, remains a major cause of maternal and neonatal mortality. The sequestration of infected erythrocytes in the placenta is mediated by the VAR2CSA protein. However, its high polymorphism complicates vaccine development. Targeting conserved sub-units like the Duffy Binding-Like 5 (DBL5) domain offers a potential alternative strategy. This study aimed to profile the immune response to the DBL5 domain and evaluate its cross-reactivity with VAR2CSA among pregnant women in Northern Ghana. MethodsA subset of 156 plasma samples was selected from a cross-sectional study of pregnant women, categorized into P. falciparum-infected, hepatitis B-infected, and co-infected groups. The DBL5 domain was recombinantly expressed in E. coli, and its immunogenicity was assessed using indirect ELISA. Immunoinformatics tools were used to predict conserved B-cell and T-cell epitopes. ResultsELISA results demonstrated significantly higher antibody reactivity to DBL5 in the P. falciparum-infected group (mean OD: 1.56 {+/-} 0.12) compared to the hepatitis B-only (0.89 {+/-} 0.15) and co-infection (1.22 {+/-} 0.18) groups (p < 0.001). This indicates a specific and robust immune response to DBL5 in malaria-exposed women. Furthermore, plasma samples showed overlapping reactivity to both DBL5 and VAR2CSA, suggesting immunogenic cross-reactivity. Epitope mapping identified conserved DBL5 epitopes with broad global population coverage (>95%). ConclusionThe DBL5 domain is highly immunogenic and demonstrates partial cross-reactivity with VAR2CSA. Our findings advocate for DBL5 as a promising, conserved candidate for inclusion in a multi-epitope vaccine against pregnancy-associated malaria.