Limited sequence polymorphisms of four transmission-blocking vaccine candidate antigens in Plasmodium vivax Korean isolates

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.

Plasmodium vivax gametocyte proteins, Pvs48/45 and Pvs47, induce transmission-reducing antibodies by DNA immunization

“…We confirmed findings that substitutions in Pvs47 are more abundant than in Pvs48/45 [43]. Overall, the polymorphisms of both Pvs48/45 and Pvs47 were much lower than those of blood stage proteins such as the merozoite surface protein-1 and the Duffy binding protein [49]. Despite the presence of polymorphisms, antibodies directed against the Sal-1 sequence (American origin) of both Pvs48/45 and Pvs47 are able to reduce transmission of two Thai isolates to mosquitoes (Fig.…”

“…Two published reports describe polymorphisms of Pvs48/45 [43,49], and one report for Pvs47 [43]. Woo et al [43] reported that Pvs48/45 of Korean vivax isolates were classified into five haplotypes (Korea 1-5 in Fig.…”

Identification of candidate transmission-blocking antigen genes in Theileria annulata and related vector-borne apicomplexan parasites

“…In contrast, genes encoding proteins specific to vector stages and not exposed to an acquired protective immune response may show more limited levels of selection for amino acid substitution [38]. To assess whether the putative proteins encoded by transmission-blocking candidate genes may be exposed to the immune response or act as hidden antigens, the level of dN/dS was computed for three candidate genes with evidence of elevated expression in tick stages.…”

Advances in genetics and genomics: use and limitations in achieving malaria elimination goals

“…200 Pvs25 and Pvs28 are two TBV candidates that have been widely studied and shown to have limited sequence polymorphisms and believed to offer great promise as TBVs against P. vivax infection. 201,202 Genetic surveillance Molecular markers of drug-resistant malaria represent public health tools of great potential value. These markers can allow tracking of the spread of resistance alleles, map the distribution and rate of spread and inform local treatment policies.…”