Genetic diversity of transmission-blocking vaccine candidates Pvs25 and Pvs28 in Plasmodium vivax isolates from Yunnan Province, China

Abstract

BackgroundTransmission-blocking vaccines (TBVs) have been considered an important strategy for disrupting the malaria transmission cycle, especially for Plasmodium vivax malaria, which undergoes gametocytogenesis earlier during infection. Pvs25 and Pvs28 are transmission-blocking vaccine candidates for P. vivax malaria. Assessment of genetic diversity of the vaccine candidates will provide necessary information for predicting the performance of vaccines, which will guide us during the development of malaria vaccines.ResultsWe sequenced the coding regions of pvs25 and pvs28 from 30 P. vivax isolates from Yunnan Province, identifying five amino acid haplotypes of Pvs25 and seven amino acid haplotypes of Pvs28. Among a total of four mutant residues, the predominant haplotype of Pvs25 only had the I130T substitution. For Pvs28, a total of eight amino acid substitutions were identified. The predominant haplotype of Pvs28 had two substitution at positions 52 (M52L) and 140 (T140S) with 5-6 GSGGE/D tandem repeats at the end of fourth EGF-like domain. Most amino acid substitutions were common with previous reports from South Asian isolates. Although the nucleotide diversity of pvs28 (π = 0.0034 ± 0.0012) was significantly higher than pvs25 (π = 0.0013 ± 0.0009), it was still conserved when compared with the blood stage vaccine candidates.ConclusionsGenetic analysis revealed limited genetic diversity of pvs25 and pvs28, suggesting antigenic diversity may not be a particular problem for Sal I based TBVs in most P. vivax-endemic areas of China.

Plasmodium vivax HAP2/GCS1 gene exhibits limited genetic diversity among parasite isolates from the Greater Mekong Subregion

“…Pvhap2 showed lower genetic diversity (ranging from 0.00018 to 0.00075 for all global isolates analyzed) [26] compared to other sexual stage transmission-blocking antigens reported in P. vivax such as pvs28/25 (π = 0.0034/0.0013, Yunnan Province of China, [43]; π = 0.0041/0.0023, Myanmar, [44]), pvs48/45 (π = 0.00173, global isolates, [45]), and pvs230 (π = 0.00118, global isolates, [46]). This high level of conservation may be a consequence of the essential function of this protein in fertilization.…”

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

“…As expected, the overall nucleotide diversities of the four TBV candidates, Pvs25 (π = 0.00065), Pvs28 (π = 0.00000), Pvs48/45 (π = 0.00053), and PvWARP (π = 0.00010), were much lower than those of blood stage proteins such as the C-terminal 42 kDa region of the merozoite surface protein-1 (PvMSP-1 42 ; π = 0.01586) [21] and the Duffy binding protein (PvDBP; π = 0.00299) [46], which were determined from the same P. vivax isolates used in this study. Previous studies have suggested that the antigenic variation of Pvs25 is more limited than that of Pvs28 [6,35]; however, in the Korean isolates, the nucleotide diversity of Pvs28 was lower than that of Pvs25, as only a single haplotype of Pvs28 was identified. Polymorphism analyses of several blood stage antigens, including MSP-1, MSP-3α, and DBP, have strongly suggest that the genetic diversity of Korean P. vivax population has rapidly disseminated in recent years [21,27-29].…”

“…Dot represent identical amino acid residue compared to Sal I. 1 [This study], 2 [37], 3 [32], 4 [35], 5 [33], 6 [ABG29073], 7 [36], 8 [31], 9 [9], 10 [32], 11 [ABG29072], 12 [31], 13 [34], 14 [32], 15 [32], 16 [32], 17 [32], 18 Signal peptide region. ( B ) Annual distribution of Pvs25 haplotypes during the study period, 1999–2010.…”

“… 1 [This study], 2 [37], 3 [35], 4 [33], 5 [31], 6 [36], 7 [9], 8 [34], 9 Signal peptide region, 10 the copy number of the GSGGE/D tandem repeats; 11 the C terminal hydrophobic region. Dot represent identical amino acid residue compared to Sal I.…”

Domestic trends in malaria research and development in China and its global influence

“…Vaccine candidate PfCP2.9 from China is listed on the WHO malaria vaccine rainbow table. And many antigens such as Pvs25 and Pvs28 were screened and tested for the development of TBV [42]. R&D on immunology/vaccines might be more promising than antimalarial drugs in China, however, continuous governmental support is essential for this time-consuming and costly battle.…”