Program in Bioinformatics and Integrative Biology; Division of Transfusion Medicine; School of Medicine
Biostatistics; Cambodia; DNA, Protozoan; *Genetic Variation; High-Throughput Nucleotide Sequencing; Malaria Vaccines; Merozoite Surface Protein 1; Molecular Sequence Data; Phylogeny; *Phylogeography; Plasmodium vivax; Protozoan Proteins; Selection, Genetic
Biodiversity | Bioinformatics | Computational Biology | Genomics | Immunity | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Infectious Disease | Parasitic Diseases | Parasitology | Translational Medical Research
Although Plasmodium vivax is a leading cause of malaria around the world, only a handful of vivax antigens are being studied for vaccine development. Here, we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens--Plasmodium vivax merozoite surface protein 1 (pvmsp-1) and Plasmodium vivax circumsporozoite protein (pvcsp). Using scalable next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of pvmsp-1 (n = 44) and the complete gene of pvcsp (n = 47) from Cambodian isolates. These sequences were then compared with global parasite populations obtained from GenBank. Using a combination of statistical and phylogenetic methods to assess for selection and population structure, we found strong evidence of balancing selection in the 42 kDa region of pvmsp-1, which varied significantly over the length of the gene, consistent with immune-mediated selection. In pvcsp, the highly variable central repeat region also showed patterns consistent with immune selection, which were lacking outside the repeat. The patterns of selection seen in both genes differed from their P. falciparum orthologs. In addition, we found that, similar to merozoite antigens from P. falciparum malaria, genetic diversity of pvmsp-1 sequences showed no geographic clustering, while the non-merozoite antigen, pvcsp, showed strong geographic clustering. These findings suggest that while immune selection may act on both vivax vaccine candidate antigens, the geographic distribution of genetic variability differs greatly between these two genes. The selective forces driving this diversification could lead to antigen escape and vaccine failure. Better understanding the geographic distribution of genetic variability in vaccine candidate antigens will be key to designing and implementing efficacious vaccines.
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DOI of Published Version
PLoS Negl Trop Dis. 2014 Apr 17;8(4):e2796. doi: 10.1371/journal.pntd.0002796. eCollection 2014. Link to article on publisher's site
PLoS neglected tropical diseases
Parobek, Christian M.; Bailey, Jeffrey A.; Hathaway, Nicholas J.; Socheat, Duong; Rogers, William O.; and Juliano, Jonathan J., "Differing patterns of selection and geospatial genetic diversity within two leading Plasmodium vivax candidate vaccine antigens" (2014). UMass Center for Clinical and Translational Science Supported Publications. 28.
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