Characterizing the antibody specificity of sera from malaria endemic African countries for sequence micro-heterogeneities within the dimorphic domain of Pf3D7-MSP2

Abstract


Saidou Balam, Nathan C Incandela, Drissa Konate, George Agak, Mahamadou Diakite, Remy Moret, Issa Nebie, Giampietro Corradin

Background: Micro-heterogenicity of 25-mer segments within the dimorphic domain (Pf3D7-D) defined various alleles of Pf3D7-type MSP2. This study explored the specificity of African malaria-endemic antibodies (IgG) to this micro-heterogenicity.  
Methods: We tested in ELISA immunoassays (standard and competitive ELISA) 12 synthetic 25-mer   peptides representing each micro-heterogenous segment using sera from Mali, ML (N=75), Burkina Faso, BF (N=49) and Tanzania, TZ (N=37).  
Findings: Overall, BF antibody samples had significantly higher affinities (p<0.0001) and the largest proportion (45%-65%) of positive responders for all the 25 mer-peptides. In contrast, ML samples had slightly lower antibody affinities and a smaller proportion of responders (15%-57%), whereas TZ sample demonstrated the lowest antibody affinities and fewest proportions of responders (3%-46%). Children 6-14 years-old exhibited higher antibody affinities and a larger proportion of responders (20%-80%) compared to ≤ 5 years-old (08-54%, p=0.001) and ≥ 15 years-old (05%-37%, p<0.0001). Furthermore, a large number of responders recognized at least one, if not all, of the 25-mer epitopes. The 25-mer peptides showed cross-inhibition with each other. 
Conclusion: This work broadened our understanding of the specificity profiles of antibodies for the Pf3D7 allele epitopes and suggested the presence of multi-genotypic Pf3D7 infections in the population. 

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