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    Differing patterns of selection and geospatial genetic diversity within two leading Plasmodium vivax candidate vaccine antigens

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    Authors
    Parobek, Christian M.
    Bailey, Jeffrey A.
    Hathaway, Nicholas J.
    Socheat, Duong
    Rogers, William O.
    Juliano, Jonathan J.
    UMass Chan Affiliations
    School of Medicine
    Division of Transfusion Medicine
    Program in Bioinformatics and Integrative Biology
    Document Type
    Journal Article
    Publication Date
    2014-04-17
    Keywords
    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
    UMCCTS funding
    Biodiversity
    Bioinformatics
    Computational Biology
    Genomics
    Immunity
    Immunology of Infectious Disease
    Immunoprophylaxis and Therapy
    Infectious Disease
    Parasitic Diseases
    Parasitology
    Translational Medical Research
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    Abstract
    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.
    Source
    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
    DOI
    10.1371/journal.pntd.0002796
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/50455
    PubMed ID
    24743266
    Related Resources
    Link to Article in PubMed
    Rights
    This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pntd.0002796
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    UMass Center for Clinical and Translational Science Supported Publications

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