Abstract
BackgroundAntigens expressed in sexual stages of the malaria parasites are targets of transmission-blocking vaccines (TBVs). HAP2/GCS1, a TBV candidate, is critical for fertilization in Plasmodium. Here, the genetic diversity of PvHAP2 was studied in Plasmodium vivax parasite populations from the Greater Mekong Subregion (GMS).MethodsPlasmodium vivax clinical isolates were collected in clinics from the China-Myanmar border region (135 samples), western Thailand (41 samples) and western Myanmar (51 samples). Near full-length Pvhap2 (nucleotides 13–2574) was amplified and sequenced from these isolates. Molecular evolution studies were conducted to evaluate the genetic diversity, selection and population differentiation.ResultsSequencing of the pvhap2 gene for a total of 227 samples from the three P. vivax populations revealed limited genetic diversity of this gene in the GMS (π = 0.00036 ± 0.00003), with the highest π value observed in Myanmar (0.00053 ± 0.00009). Y133S was the dominant mutation in the China-Myanmar border (99.26%), Myanmar (100%) and Thailand (95.12%). Results of all neutrality tests were negative for all the three populations, suggesting the possible action of purifying selection. Codon-based tests identified specific codons which are under purifying or positive selections. Wright’s fixation index showed low to moderate genetic differentiation of P. vivax populations in the GMS, with FST ranging from 0.04077 to 0.24833, whereas high levels of genetic differentiation were detected between the China-Myanmar border and Iran populations (FST = 0.60266), and between Thailand and Iran populations (FST = 0.44161). A total of 20 haplotypes were identified, with H2 being the abundant haplotype in China-Myanmar border, Myanmar and Thailand populations. Epitope mapping prediction of Pvhap2 antigen showed that high-score B-cell epitopes are located in the S307-G324, L429-P453 and V623-D637 regions. The E317K and D637N mutations located within S307-G324 and V623-D637 epitopes slightly reduced the predicted score for potential epitopes.ConclusionsThe present study showed a very low level of genetic diversity of pvhap2 gene among P. vivax populations in the Greater Mekong Subregion. The relative conservation of pvhap2 supports further evaluation of a Pvhap2-based TBV.
Highlights
Antigens expressed in sexual stages of the malaria parasites are targets of transmission-blocking vaccines (TBVs)
The genetic diversity, natural selection, population differentiation and haplotype prevalence of Pvhap2 in P. vivax populations from the Greater Mekong Subregion (GMS) were assessed in this study. These analyses revealed limited genetic diversity of Pvhap2 gene as well as little differentiation of parasite populations in the GMS compared with the global sequences of a gamete fertilization essential gene, so as to provide useful information for transmission blocking vaccine development
Polymorphism in the pvhap2 gene We sequenced the almost full-length pvhap2 gene in 227 clinical P. vivax samples collected from three regions of the GMS
Summary
Antigens expressed in sexual stages of the malaria parasites are targets of transmission-blocking vaccines (TBVs). Li et al Parasites Vectors (2020) 13:175 programme in the GMS has led to a steady decline of malaria burden in the GMS in recent years [2]. This ambitious plan encounters multiple challenges such as antimalarial multidrug resistance, cross-border population mobility and parasite introduction, and asymptomatic Plasmodium infections as the reservoir for malaria transmission [3,4,5,6]. Transmission-blocking vaccines (TBVs) are considered an integral component of the measures for malaria control and elimination [8,9,10,11]
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