Abstract
BackgroundPlasmodium vivax apical membrane antigen-1 (PvAMA-1) is a leading candidate antigen for blood stage malaria vaccine. However, antigenic variation is a major obstacle in the development of an effective vaccine based on this antigen. In this study, the genetic structure and the effect of natural selection of PvAMA-1 among Korean P. vivax isolates were analysed.MethodsBlood samples were collected from 66 Korean patients with vivax malaria. The entire PvAMA-1 gene was amplified by polymerase chain reaction and cloned into a TA cloning vector. The PvAMA-1 sequence of each isolate was sequenced and the polymorphic characteristics and effect of natural selection were analysed using the DNASTAR, MEGA4, and DnaSP programs.ResultsThirty haplotypes of PvAMA-1, which were further classified into seven different clusters, were identified in the 66 Korean P. vivax isolates. Domain II was highly conserved among the sequences, but substantial nucleotide diversity was observed in domains I and III. The difference between the rates of non-synonymous and synonymous mutations suggested that the gene has evolved under natural selection. No strong evidence indicating balancing or positive selection on PvAMA-1 was identified. Recombination may also play a role in the resulting genetic diversity of PvAMA-1.ConclusionsThis study is the first comprehensive analysis of nucleotide diversity across the entire PvAMA-1 gene using a single population sample from Korea. Korean PvAMA-1 had limited genetic diversity compared to PvAMA-1 in global isolates. The overall pattern of genetic polymorphism of Korean PvAMA-1 differed from other global isolates and novel amino acid changes were also identified in Korean PvAMA-1. Evidences for natural selection and recombination event were observed, which is likely to play an important role in generating genetic diversity across the PvAMA-1. These results provide useful information for the understanding the population structure of P. vivax circulating in Korea and have important implications for the design of a vaccine incorporating PvAMA-1.
Highlights
Plasmodium vivax apical membrane antigen-1 (PvAMA-1) is a leading candidate antigen for blood stage malaria vaccine
Sequence polymorphism in Korean PvAMA‐1 Sixty-six PvAMA-1 sequences with 30 different haplotypes were obtained from Korean P. vivax isolates
Nucleotide sequence analysis of the 66 sequences compared to SalI (AF063138) revealed 66 single nucleotide polymorphisms (SNPs) in the Korean PvAMA-1 sequences
Summary
Plasmodium vivax apical membrane antigen-1 (PvAMA-1) is a leading candidate antigen for blood stage malaria vaccine. Plasmodium vivax is the most prevalent human malaria parasite globally and is responsible for a large proportion of the global malaria burden, especially in regions outside of Africa [1]. It has been neglected as a benign infection, P. vivax causes serious clinical illnesses including respiratory distress, severe anemia, coma and even death [2, 3]. It has recently re-emerged in many temperate regions from where it had been largely eradicated during global malaria control campaigns. No effective vaccine is yet available and the antigenic diversity present in wild-type isolates, which has led to the failure of several licensed and tested malaria vaccines, has been recognized as a major concern in developing a successful vaccine
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