Plasmodium vivax Duffy Binding Protein domain II from Nicaragua depicts low diversity, and the persistent haplotypes mirror those globally. Molecular polymorphism of Plasmodium vivax Duffy Binding Protein domain II from Nicaragua, and global diversity patterns

LILIA GONZALEZ-CERON^1*Rene Ortega-Muñoz²Hugo A Tomasini-Ovilla²FRIDA SANTILLAN²Alberto Montoya³

• ¹Department of Health systems, Regional Center of Research in Public Health, National Institute of Public Health, Ministry of Health, Tapachula, Mexico, Tapachula, Mexico
• ²Regional Center of Research in Public Health, National Institute of Public Health, Ministry of Health, Tapachula, Mexico
• ³Parasitology Department, National Centre for Diagnosis Reference, Ministry of Health., Managua, Nicaragua

Background: Plasmodium vivax Duffy antigen-binding protein domain II (PvBDPII) is a promising vaccine candidate, due to its crucial role in reticulocyte invasion. However, there is a concern about polymorphism conferring evasion of blocking antibodies. In this study, the nucleotide and protein polymorphism of this protein was analyzed in parasites collected during a decline in malaria cases in Nicaragua.Methods: Genomic DNA was extracted from P. vivax infected blood samples obtained from symptomatic patients in Nicaragua, 2012-2013. PvdbpII gene was amplified and sequenced by Sanger method, and the genetic structure, genealogical relationships, and amino acid polymorphism were analyzed. For comparisons and to elucidate the current global variation of this gene, homologous sequences from other geographical regions were included in the analysis.Results: Sixty-three pvdbpII consensus sequences from Nicaragua were obtained and revealed 12 nonsynonymous mutations, and 6 haplotypes (Hd=0.704). The Nucleotide diversity was lower (=0.0044) than that in other affected regions. The Z test of selection (dN/dS) was positive (3.17; p < 0.001) similar to other parasite populations worldwide (Latin America, Middle East, Asia, Southeast Asia, Africa, PNG). Network analysis revealed that pvdbpII haplotypes from Nicaragua differed by 3 to 12 mutational steps. High-frequency haplotypes from six other countries in Latin America were shared with signs of diversification, and limited population sStructure. While five Nicaraguan haplotypes correspond to the 10 most frequent globally, haplotypes defined solely by amino acid changes at positions 417, 437, and 503, were of the Sal-I type (NWI), NWK and KRK. Those along with KRI were shared across most regions at varying frequencies. Based on those variations, two main divergent groups were identified.The low diversity observed in pvdbpII suggests a population contraction that aligns with the decline of malaria cases in Nicaragua during the sampling period. Consequently, the PvDBPII haplotypes found may represent those that are better adapted in Nicaragua and other affected regions in Latin America and globally, encompassing both Sal-I-related and divergent types. It would be beneficial to assess the capacity of the most frequent and persistent phenotypes to elicit phenotypetranscending immunity for the development of a multicomponent vaccine and for monitoring its effectiveness.