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dc.contributor.authorParobek, Christian M.
dc.contributor.authorBailey, Jeffrey A.
dc.contributor.authorHathaway, Nicholas J
dc.contributor.authorSocheat, Duong
dc.contributor.authorRogers, William O.
dc.contributor.authorJuliano, Jonathan J.
dc.date2022-08-11T08:11:03.000
dc.date.accessioned2022-08-23T17:30:07Z
dc.date.available2022-08-23T17:30:07Z
dc.date.issued2014-04-17
dc.date.submitted2014-11-27
dc.identifier.citationPLoS Negl Trop Dis. 2014 Apr 17;8(4):e2796. doi: 10.1371/journal.pntd.0002796. eCollection 2014. <a href="http://dx.doi.org/10.1371/journal.pntd.0002796">Link to article on publisher's site</a>
dc.identifier.issn1935-2727 (Linking)
dc.identifier.doi10.1371/journal.pntd.0002796
dc.identifier.pmid24743266
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50455
dc.description.abstractAlthough 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24743266&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsThis 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.
dc.subjectBiostatistics
dc.subjectCambodia
dc.subjectDNA, Protozoan
dc.subject*Genetic Variation
dc.subjectHigh-Throughput Nucleotide Sequencing
dc.subjectMalaria Vaccines
dc.subjectMerozoite Surface Protein 1
dc.subjectMolecular Sequence Data
dc.subjectPhylogeny
dc.subject*Phylogeography
dc.subjectPlasmodium vivax
dc.subjectProtozoan Proteins
dc.subjectSelection, Genetic
dc.subjectUMCCTS funding
dc.subjectBiodiversity
dc.subjectBioinformatics
dc.subjectComputational Biology
dc.subjectGenomics
dc.subjectImmunity
dc.subjectImmunology of Infectious Disease
dc.subjectImmunoprophylaxis and Therapy
dc.subjectInfectious Disease
dc.subjectParasitic Diseases
dc.subjectParasitology
dc.subjectTranslational Medical Research
dc.titleDiffering patterns of selection and geospatial genetic diversity within two leading Plasmodium vivax candidate vaccine antigens
dc.typeJournal Article
dc.source.journaltitlePLoS neglected tropical diseases
dc.source.volume8
dc.source.issue4
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1027&amp;context=umccts_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/umccts_pubs/28
dc.identifier.contextkey6400416
refterms.dateFOA2022-08-23T17:30:07Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathumccts_pubs/28
dc.contributor.departmentSchool of Medicine
dc.contributor.departmentDivision of Transfusion Medicine
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology
dc.source.pagese2796


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