Evaluation of two Plasmodium vivax sexual stage antigens as transmission-blocking vaccine candidates

Yongzhe Zhang,Yaming Cao,Liwang Cui,Jie Bai,Jetsumon Sattabongkot,Xitong Jia,Fan Yang,Wanlapa Roobsoong,Meilian Wang,Fei Liu,Yan Zhao,Enjie Luo

doi:10.1186/s13071-021-04909-w

Abstract

BackgroundPlasmodium vivax transmission-blocking vaccines (TBVs) are receiving increasing attention. Based on excellent transmission-blocking activities of the PbPH (PBANKA_0417200) and PbSOP26 (PBANKA_1457700) antigens in Plasmodium berghei, their orthologs in P. vivax, PVX_098655 (PvPH) and PVX_101120 (PvSOP26), were selected for the evaluation of their potential as TBVs.MethodsFragments of PvPH (amino acids 22–304) and PvSOP26 (amino acids 30–272) were expressed in the yeast expression system. The recombinant proteins were used to immunize mice to obtain antisera. The transmission-reducing activities of these antisera were evaluated using the direct membrane feeding assay (DMFA) using Anopheles dirus mosquitoes and P. vivax clinical isolates.ResultsThe recombinant proteins PvPH and PvSOP26 induced robust antibody responses in mice. The DMFA showed that the anti-PvSOP26 sera significantly reduced oocyst densities by 92.0 and 84.1% in two parasite isolates, respectively, whereas the anti-PvPH sera did not show evident transmission-reducing activity. The variation in the DMFA results was unlikely due to the genetic polymorphisms of the two genes since their respective sequences were identical in the clinical P. vivax isolates.ConclusionPvSOP26 could be a promising TBV candidate for P. vivax, which warrants further evaluation.Graphical

Highlights

Plasmodium vivax transmission-blocking vaccines (TBVs) are receiving increasing attention
Antigen selection and expression in yeast Based on the excellent transmission-reducing (TR) activities of PbPH (PBANKA_0417200) and PbSOP26 (PBANKA_1457700) in P. berghei [20, 21], their orthologs in P. vivax, PVX_098655 (PvPH) and PVX_101120 (PvSOP26), were selected for evaluation
A 282aa fragment (22–304 aa) of PvPH and a 242-aa fragment (30–272 aa) of PvSOP26 were selected for expression in the yeast P. pastoris (Fig. 1a)

Summary

Introduction

Plasmodium vivax transmission-blocking vaccines (TBVs) are receiving increasing attention. The malaria parasite life-cycle is complex and, multi-stage vaccines targeting antigens expressed. Transmission-blocking vaccines (TBVs) target the parasite’s sexual stage antigens or the mosquito’s midgut antigens, interrupting the parasite’s transmission through mosquitoes. Despite decades of research efforts, only a few TBV candidates have shown clear transmission-blocking (TB) activities. These TBV candidates mainly include the pre-fertilization antigens (P230, P48/45, P47 and HAP2) [8,9,10,11], the post-fertilization antigens (P25 and P28) [12] and the Anopheles mosquito midgut alanyl aminopeptidase N (AnAPN1) [13, 14]. There is a pressing need to identify additional TBV candidates for P. vivax

Methods

Results

Discussion

Conclusion