Genetic diversity of the malaria vaccine candidate merozoite surface protein 1 gene of Plasmodium vivax field isolates in Republic of Korea

Han, Eun Taek; Wang, Yue; Lim, Chae Seung; Cho, Jun Hwi; Chai, Jong Yil

doi:10.1007/s00436-011-2413-5

Cited by 12 publications

(5 citation statements)

References 32 publications

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“…The population sets included in this survey were collected in different years. While it is known that novel P. vivax surface antigen types can appear in the course of a decade [57], it is difficult to assess the magnitude of this effect on our analyses. As more pvmsp-1 and pvcsp population sets are collected, this will become clearer.…”

Section: Discussionmentioning

confidence: 99%

Differing Patterns of Selection and Geospatial Genetic Diversity within Two Leading Plasmodium vivax Candidate Vaccine Antigens

et al. 2014

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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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Section: Discussionmentioning

confidence: 99%

Differing Patterns of Selection and Geospatial Genetic Diversity within Two Leading Plasmodium vivax Candidate Vaccine Antigens

et al. 2014

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“…Homologous DNA sequences from other geographic sites were obtained from the NCBI GenBank: Msp1 42 . For South Korea (SK), n = 200: JQ446312-JQ446322 [ 41 ], HQ171934-HQ171941 [ 42 ], and AF435635-AF435638 [ 11 ]. For Turkey (TUR), n = 30: AB564559-AB564588 [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

Diversity and evolutionary genetics of the three major Plasmodium vivax merozoite genes participating in reticulocyte invasion in southern Mexico

et al. 2015

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BackgroundReported malaria cases in the Americas had been reduced to about one-half million by 2012. To advance towards elimination of this disease, it is necessary to gain insights into how the malaria parasite is evolving, including the emergence, spread and persistence of new haplotypes in affected regions. In here, the genetic diversity of the three major P. vivax merozoite genes was analyzed.MethodsFrom P. vivax-infected blood samples obtained in southern Mexico (SMX) during 2006–2007, nucleotide sequences were achieved for: the 42 kDa carboxyl fragment of the merozoite surface protein-1 (msp142), domains I-II of the apical membrane antigen-1 (ama1I-II), and domain II of the Duffy binding protein (dbpII). Gene polymorphism was examined and haplotype networks were developed to depict parasite relationships in SMX. Then genetic diversity, recombination and natural selection were analyzed and the degree of differentiation was determined as FST values.ResultsThe diversity of P. vivax merozoite genes in SMX was less than that of parasites from other geographic origins, with dbpII < ama1I-II < msp142. Ama1I-II and msp142 exposed the more numerous haplotypes exclusive to SMX. While, all dbpII haplotypes from SMX were separated from one to three mutational steps, the networks of ama1I-II and msp142 were more complex; loops and numerous mutational steps were evidenced, likely due to recombination. Sings of local diversification were more evident for msp142. Sixteen combined haplotypes were determined; one of these haplotypes not detected in 2006 was highly frequent in 2007. The Rm value was higher for msp142than for ama1I-II, being insignificant for dbpII. The dN-dS value was highly significant for ama1I-II and lesser so for dbpII. The FST values were higher for dbpII than msp142, and very low for ama1I-II.ConclusionsIn SMX, P. vivax ama1I-II, dbpII and msp142 demonstrated limited diversity, and exhibited a differentiated parasite population. The results suggest that differential intensities of selective forces are operating on these gene fragments, and probably related to their timing, length of exposure and function during reticulocyte adhesion and invasion. Therefore, these finding are essential for mono and multivalent vaccine development and for epidemiological surveillance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-1266-7) contains supplementary material, which is available to authorized users.

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“…quent meiotic recombination events that shuffle different sequence types to generate new alleles are responsible for the mosaic structure of PvMSP-1 (Putaporntip et al 1997(Putaporntip et al , 2002. Recently, Han et al (2011) compared PvMSP-1 alleles from re-emergent P. vivax parasites collected in the Republic of Korea over the past decade. They showed an increase in allelic diversity for variable domains of this protein, suggesting that recombination independently changed protein domains.…”

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confidence: 99%

Molecular markers and genetic diversity of Plasmodium vivax

Brito

Ferreira

2011

Mem. Inst. Oswaldo Cruz

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Enhanced understanding of the transmission dynamics and population genetics for Key words: malaria -Plasmodium vivax -genetic markers -genetic diversity -multiple-clone infections -microsatellitesMarkers and genetic diversity of P. vivax • Cristiana Ferreira Alves de Brito, Marcelo Urbano Ferreira 13 tual heterozygosity (H E ) values. Virtual H E is the average probability that a pair of alleles randomly obtained from the population is different. Whenever appropriate, in this review we provide H E estimates obtained using different markers for different populations.Molecular markers under selection -Until recently, most genetic markers available for characterising natural P. vivax populations were orthologues of previously identified P. falciparum antigen-coding genes. The wellcharacterised polymorphic regions in these genes have been extensively used to analyse genetic diversity patterns in P. falciparum (Roy et al. 2008). A similar approach has been explored in vivax-oriented studies (Cui et al. 2003a). The following single-copy genes in P. vivax have often been used in these studies: gam1, coding for the gametocyte antigen 1, csp, coding for the circumsporozoite protein (CSP), msp1 and msp3alpha, coding for the merozoite surface proteins (MSP)-1 and 3α, respectively, ama1, coding for the apical membrane antigen 1, and dbp, coding for the Duffy binding protein (DBP) ( Table I).A notable feature of several P. vivax surface antigens (including major vaccine-candidate molecules) is tandem arrays of relatively short amino acid motifs. The CSP in P. vivax (PvCSP), an abundant antigen on the surface of sporozoites that has been extensively used as a vaccine development target, has immunodominant B-cell epitopes that map to central repeats between nonrepetitive sequences (Nardin & Zavala 1998). PvCSP displays two major types of nonapeptide repeats [most commonly GDRA(D/A)GQPA and ANGA(G/D)(N/D)QPG], which define the variants known as VK210 and VK247, respectively (Arnot et al. 1985, Rosenberg et al. 1989 (Fig. 1). Both VK210 and VK247 variants are globally distributed, but geographic biases have been described (Cochrane et al. 1990, Qari et al. 1993a. Similar repetitive sequences are found in Brazil, Southeast Asia and Papua New Guinea (Qari et al. 1991(Qari et al. , 1992. However, markedly divergent sequence variants were found in isolates from China and North Korea (Mann et al. 1994). Although VK210 and VK247-type sequences often occur in sympatric parasite populations, there are no examples of a hybrid repeat array with both repeat types (Lim et al. 2005).A third type of repeat unit [APGANQ(E/G)GAA], identical to that described for Plasmodium simiovale, characterises the so-called P. vivax-like parasites (Qari et al. 1993a). Although P. vivax-like CSP repeats have been found in parasite isolates across the world, its global distribution remains unconfirmed (Gopinath et al. 1994). In Brazil, P. vivax-like parasites have been identified only in mixed-clone infections with VK210-type or VK247-type parasites (Machado...

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Genetic diversity of the malaria vaccine candidate merozoite surface protein 1 gene of Plasmodium vivax field isolates in Republic of Korea

Cited by 12 publications

References 32 publications

Differing Patterns of Selection and Geospatial Genetic Diversity within Two Leading Plasmodium vivax Candidate Vaccine Antigens

Differing Patterns of Selection and Geospatial Genetic Diversity within Two Leading Plasmodium vivax Candidate Vaccine Antigens

Diversity and evolutionary genetics of the three major Plasmodium vivax merozoite genes participating in reticulocyte invasion in southern Mexico

Molecular markers and genetic diversity of Plasmodium vivax

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