Global distribution of single amino acid polymorphisms in Duffy-binding-like domain and implications for vaccine development efforts.

() malaria continues to be geographically widespread with approximately 15 million worldwide cases annually. Along with other proteins, Duffy-binding proteins (DBPs) are used by plasmodium for RBC invasion and the parasite-encoded receptor binding regions lie in their Duffy-binding-like (DBL) domains-thus making it a prime vaccine candidate. This study explores the sequence diversity in DBL globally, with an emphasis on India as it remains a major contributor to the global malaria burden. Based on 1358 DBL protein sequences available in NCBI, we identified 140 polymorphic sites within 315 residues of DBL. Alarmingly, country-wise mapping of SAAPs from field isolates revealed varied and distinct polymorphic profiles for different nations. We report here 31 polymorphic residue positions in the global SAAP profile, most of which map to the DBL subdomain 2 (1-6). A distinct clustering of SAAPs distal to the DARC-binding sites is indicative of immune evasive strategies by the parasite. Analyses of DBL-neutralizing antibody complexes revealed that between 24% and 54% of interface residues are polymorphic. This work provides a framework to recce and expand the polymorphic space coverage in DBLs as this has direct implications for vaccine development studies. It also emphasizes the significance of surveying global SAAP distributions before or alongside the identification of vaccine candidates.