Differing patterns of selection and geospatial genetic diversity within two leading Plasmodium vivax candidate vaccine antigens
Authors
Parobek, Christian M.Bailey, Jeffrey A.
Hathaway, Nicholas J.
Socheat, Duong
Rogers, William O.
Juliano, Jonathan J.
UMass Chan Affiliations
School of MedicineDivision of Transfusion Medicine
Program in Bioinformatics and Integrative Biology
Document Type
Journal ArticlePublication Date
2014-04-17Keywords
BiostatisticsCambodia
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
Metadata
Show full item recordAbstract
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 siteDOI
10.1371/journal.pntd.0002796Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50455PubMed ID
24743266Related Resources
Link to Article in PubMedRights
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