Genetic diversity in the transmission-blocking vaccine candidate Plasmodium vivax gametocyte protein Pvs230 from the China–Myanmar border area and central Myanmar

Abstract

AbstractBackgroundSexual stage surface antigens are potential targets of transmission-blocking vaccines (TBVs). The gametocyte and gamete surface antigen P230, a leading TBV candidate, is critical for red blood cell binding during exflagellation and subsequent oocyst development. Here, the genetic diversity ofPvs230was studied inPlasmodium vivaxparasite isolates from the China–Myanmar border (CMB) and central Myanmar.MethodsPlasmodium vivaxisolates were collected in clinics from malaria-endemic areas of the CMB (143 samples) and Myanmar (23 samples). The interspecies variable part (IVP, nucleotides 1–807) and interspecies conserved part (ICP, 808–2862) ofPvs230were amplified by PCR and sequenced. Molecular evolution studies were conducted to evaluate the genetic diversity, signature of selection, population differentiation, haplotype network, and population structure of the study parasite populations and publicly availablePvs230sequences from six globalP. vivaxpopulations.ResultsLimited genetic diversity was observed for the CMB (π = 0.002) and Myanmar (π = 0.001) isolates. Most amino acid substitutions were located in the IVP and cysteine-rich domain ofPvs230. Evidence of positive selection was observed for IVP and purifying selection for ICP. Codon-based tests identified specific codons under natural selection in both IVP and ICP. The fixation index (FST) showed low genetic differentiation between East and Southeast Asian populations, withFSTranging from 0.018 to 0.119. The highestFSTvalue (FST = 0.503) was detected between the Turkey and Papua New Guinea populations. A total of 92 haplotypes were identified in global isolates, with the major haplotypes 2 and 9 being the most abundant and circulating in East and Southeast Asia populations. Several detected non-synonymous substitutions were mapped in the predicted structure and B-cell epitopes of Pvs230.ConclusionsWe detected low levels of genetic diversity ofPvs230in globalP. vivaxpopulations. Geographically specific haplotypes were identified forPvs230. Some mutations are located within a potential B-cell epitope region and need to be considered in future TBV designs.Graphical Abstract