Abstract
BackgroundTransmission-blocking vaccines (TBVs), which target the sexual stages of malaria parasites to interfere with and/or inhibit the parasite’s development within mosquitoes, have been regarded as promising targets for disrupting the malaria transmission cycle. In this study, genetic diversity of four TBV candidate antigens, Pvs25, Pvs28, Pvs48/45, and PvWARP, among Plasmodium vivax Korean isolates was analysed.MethodsA total of 86 P. vivax-infected blood samples collected from patients in Korea were used for analyses. Each of the full-length genes encoding four TBV candidate antigens, Pvs25, Pvs28, Pvs48/45, and PvWARP, were amplified by PCR, cloned into T&A vector, and then sequenced. Polymorphic characteristics of the genes were analysed using the DNASTAR, MEGA4, and DnaSP programs.ResultsPolymorphism analyses of the 86 Korean P. vivax isolates revealed two distinct haplotypes in Pvs25 and Pvs48/45, and three different haplotypes in PvWARP. In contrast, Pvs28 showed only a single haplotype. Most of the nucleotide substitutions and amino acid changes identified in all four TBV candidate antigens were commonly found in P. vivax isolates from other geographic areas. The overall nucleotide diversities of the TBV candidates were much lower than those of blood stage antigens.ConclusionsLimited sequence polymorphisms of TBV candidate antigens were identified in the Korean P. vivax population. These results provide baseline information for developing an effective TBV based on these antigens, and offer great promise for applications of a TBV against P. vivax infection in regions where the parasite is most prevalent.
Highlights
Transmission-blocking vaccines (TBVs), which target the sexual stages of malaria parasites to interfere with and/or inhibit the parasite’s development within mosquitoes, have been regarded as promising targets for disrupting the malaria transmission cycle
Several recent studies have strongly suggested that the genetic diversity of P. vivax Korean isolates has rapidly disseminated in recent years [21,27,28,29], and that local transmission of the parasite is possibly established in South Korea
Pvs25 consists of three parts, which are characterized by an N-terminal signal peptide sequence followed by four epidermal growth factor (EGF)like domains and a glycosylphosphatidylinositol (GPI) anchor [6]
Summary
Transmission-blocking vaccines (TBVs), which target the sexual stages of malaria parasites to interfere with and/or inhibit the parasite’s development within mosquitoes, have been regarded as promising targets for disrupting the malaria transmission cycle. Pvs and Pvs, the most extensively studied TBV candidate antigens of P. vivax, are expressed on the surfaces of the zygotes and ookinetes of the malaria parasite [6], and play an essential role in both the survival of ookinetes in the mosquito midgut and in the subsequent penetration of the midgut epithelium and transformation into oocysts [7] These proteins have been shown to exhibit strong immunogenicities and potent transmission blocking activities [8,9,10,11,12,13], supporting their potential for TBVs. More recently, several other P. vivax proteins have been identified and partially characterized as potential antigens for a mosquito-stage TBV, including Pvs230 [14,15], chitinase (PvCHT1) [16,17], the circumsporozoite thrombospondin-related anonymous protein-related protein (PvCTRP) [18], and the von Willebrand factor A domain-related protein (PvWARP) [19,20]. Identifying genetic variations in sexual stage antigen genes among the P. vivax population is an important task for designing effective anti-malarial control measures
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