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Global Population Structure of the Genes Encoding the Malaria Vaccine Candidate, Plasmodium vivax Apical Membrane Antigen 1 (PvAMA1).

Arnott A, Mueller I, Ramsland PA, Siba PM, Reeder JC, Barry AE - PLoS Negl Trop Dis (2013)

Bottom Line: The PNG haplotypes form a distinct group of clusters not found in any other geographic region.Vaccine haplotypes were rare and geographically restricted, suggesting potentially poor efficacy of candidate PvAMA1 vaccines.It may be possible to cover the existing global PvAMA1 diversity by selection of diverse alleles based on these analyses however it will be important to first define the relationships between the genetic and antigenic diversity of this molecule.

View Article: PubMed Central - PubMed

Affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.

ABSTRACT

Background: The Plasmodium vivax Apical Membrane Antigen 1 (PvAMA1) is a promising malaria vaccine candidate, however it remains unclear which regions are naturally targeted by host immunity and whether its high genetic diversity will preclude coverage by a monovalent vaccine. To assess its feasibility as a vaccine candidate, we investigated the global population structure of PvAMA1.

Methodology and principal findings: New sequences from Papua New Guinea (PNG, n = 102) were analysed together with published sequences from Thailand (n = 158), India (n = 8), Sri Lanka (n = 23), Venezuela (n = 74) and a collection of isolates from disparate geographic locations (n = 8). A total of 92 single nucleotide polymorphisms (SNPs) were identified including 22 synonymous SNPs and 70 non-synonymous (NS) SNPs. Polymorphisms and signatures of balancing (positive Tajima's D and low FST values) selection were predominantly clustered in domain I, suggesting it is a dominant target of protective immune responses. To estimate global antigenic diversity, haplotypes comprised of (i) non-singleton (n = 40) and (ii) common (≥10% minor allele frequency, n = 23) polymorphic amino acid sites were then analysed revealing a total of 219 and 210 distinct haplotypes, respectively. Although highly diverse, the 210 haplotypes comprised of only common polymorphisms were grouped into eleven clusters, however substantial geographic differentiation was observed, and this may have implications for the efficacy of PvAMA1 vaccines in different malaria-endemic areas. The PNG haplotypes form a distinct group of clusters not found in any other geographic region. Vaccine haplotypes were rare and geographically restricted, suggesting potentially poor efficacy of candidate PvAMA1 vaccines.

Conclusions: It may be possible to cover the existing global PvAMA1 diversity by selection of diverse alleles based on these analyses however it will be important to first define the relationships between the genetic and antigenic diversity of this molecule.

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Related in: MedlinePlus

Network analysis of PvAMA1 haplotypes.Haplotypes composed of 23 common amino acid polymorphisms were analysed using the Median Joining algorithm implemented in Phylogenetic Network version 4.6.1.1 software. Nodes represent the haplotypes and lines indicate connections between them. The size of each node indicates haplotype frequency. Colours indicated by the key depict the cluster membership as defined by Structure analyses.
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pntd-0002506-g006: Network analysis of PvAMA1 haplotypes.Haplotypes composed of 23 common amino acid polymorphisms were analysed using the Median Joining algorithm implemented in Phylogenetic Network version 4.6.1.1 software. Nodes represent the haplotypes and lines indicate connections between them. The size of each node indicates haplotype frequency. Colours indicated by the key depict the cluster membership as defined by Structure analyses.

Mentions: The 210 unique 23-mer haplotypes formed a dense network with extremely complex relationships (Figure 6) however reducing the sample set to haplotypes with a frequency >1 revealed a more segmented network (Figure S6). Branching patterns in both networks correlated well with the cluster analyses described above and thus the country of origin, and ties between clusters were punctuated by admixed haplotypes (Figure 6, S6). A large number of admixed haplotypes were lost from the second network showing that these are mostly rare haplotypes and thus may be new recombinants (Figure S6). Interestingly, clusters from the South American and Asian populations overlapped, whereas all three clusters found in PNG were found in a distinct region of the network. This showed that PNG forms a distinct group of clusters more closely related to each other than clusters found in other parts of the world (Figure 6).


Global Population Structure of the Genes Encoding the Malaria Vaccine Candidate, Plasmodium vivax Apical Membrane Antigen 1 (PvAMA1).

Arnott A, Mueller I, Ramsland PA, Siba PM, Reeder JC, Barry AE - PLoS Negl Trop Dis (2013)

Network analysis of PvAMA1 haplotypes.Haplotypes composed of 23 common amino acid polymorphisms were analysed using the Median Joining algorithm implemented in Phylogenetic Network version 4.6.1.1 software. Nodes represent the haplotypes and lines indicate connections between them. The size of each node indicates haplotype frequency. Colours indicated by the key depict the cluster membership as defined by Structure analyses.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3814406&req=5

pntd-0002506-g006: Network analysis of PvAMA1 haplotypes.Haplotypes composed of 23 common amino acid polymorphisms were analysed using the Median Joining algorithm implemented in Phylogenetic Network version 4.6.1.1 software. Nodes represent the haplotypes and lines indicate connections between them. The size of each node indicates haplotype frequency. Colours indicated by the key depict the cluster membership as defined by Structure analyses.
Mentions: The 210 unique 23-mer haplotypes formed a dense network with extremely complex relationships (Figure 6) however reducing the sample set to haplotypes with a frequency >1 revealed a more segmented network (Figure S6). Branching patterns in both networks correlated well with the cluster analyses described above and thus the country of origin, and ties between clusters were punctuated by admixed haplotypes (Figure 6, S6). A large number of admixed haplotypes were lost from the second network showing that these are mostly rare haplotypes and thus may be new recombinants (Figure S6). Interestingly, clusters from the South American and Asian populations overlapped, whereas all three clusters found in PNG were found in a distinct region of the network. This showed that PNG forms a distinct group of clusters more closely related to each other than clusters found in other parts of the world (Figure 6).

Bottom Line: The PNG haplotypes form a distinct group of clusters not found in any other geographic region.Vaccine haplotypes were rare and geographically restricted, suggesting potentially poor efficacy of candidate PvAMA1 vaccines.It may be possible to cover the existing global PvAMA1 diversity by selection of diverse alleles based on these analyses however it will be important to first define the relationships between the genetic and antigenic diversity of this molecule.

View Article: PubMed Central - PubMed

Affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.

ABSTRACT

Background: The Plasmodium vivax Apical Membrane Antigen 1 (PvAMA1) is a promising malaria vaccine candidate, however it remains unclear which regions are naturally targeted by host immunity and whether its high genetic diversity will preclude coverage by a monovalent vaccine. To assess its feasibility as a vaccine candidate, we investigated the global population structure of PvAMA1.

Methodology and principal findings: New sequences from Papua New Guinea (PNG, n = 102) were analysed together with published sequences from Thailand (n = 158), India (n = 8), Sri Lanka (n = 23), Venezuela (n = 74) and a collection of isolates from disparate geographic locations (n = 8). A total of 92 single nucleotide polymorphisms (SNPs) were identified including 22 synonymous SNPs and 70 non-synonymous (NS) SNPs. Polymorphisms and signatures of balancing (positive Tajima's D and low FST values) selection were predominantly clustered in domain I, suggesting it is a dominant target of protective immune responses. To estimate global antigenic diversity, haplotypes comprised of (i) non-singleton (n = 40) and (ii) common (≥10% minor allele frequency, n = 23) polymorphic amino acid sites were then analysed revealing a total of 219 and 210 distinct haplotypes, respectively. Although highly diverse, the 210 haplotypes comprised of only common polymorphisms were grouped into eleven clusters, however substantial geographic differentiation was observed, and this may have implications for the efficacy of PvAMA1 vaccines in different malaria-endemic areas. The PNG haplotypes form a distinct group of clusters not found in any other geographic region. Vaccine haplotypes were rare and geographically restricted, suggesting potentially poor efficacy of candidate PvAMA1 vaccines.

Conclusions: It may be possible to cover the existing global PvAMA1 diversity by selection of diverse alleles based on these analyses however it will be important to first define the relationships between the genetic and antigenic diversity of this molecule.

Show MeSH
Related in: MedlinePlus