Abstract
BackgroundPlasmodium ookinete surface proteins as post-fertilization target antigens are potential malaria transmission-blocking vaccine (TBV) candidates. Putative secreted ookinete protein 25 (PSOP25) is a highly conserved ookinete surface protein, and has been shown to be a promising novel TBV target. Here, we further investigated the TBV activities of the full-length recombinant PSOP25 (rPSOP25) protein in Plasmodium berghei, and characterized the potential functions of PSOP25 during the P. berghei life-cycle.MethodsWe expressed the full-length P. berghei PSOP25 protein in a prokaryotic expression system, and developed polyclonal mouse antisera and a monoclonal antibody (mAb) against the recombinant protein. Indirect immunofluorescence assay (IFA) and Western blot were used to test the specificity of antibodies. The transmission-blocking (TB) activities of antibodies were evaluated by the in vitro ookinete conversion assay and by direct mosquito feeding assay (DFA). Finally, the function of PSOP25 during Plasmodium development was studied by deleting the psop25 gene.ResultsBoth polyclonal mouse antisera and anti-rPSOP25 mAb recognized the PSOP25 proteins in the parasites, and IFA showed the preferential expression of PSOP25 on the surface of zygotes, retorts and mature ookinetes. In vitro, these antibodies significantly inhibited ookinetes formation in an antibody concentration-dependent manner. In DFA, mice immunized with the rPSOP25 and those receiving passive transfer of the anti-rPSOP25 mAb reduced the prevalence of mosquito infection by 31.2 and 26.1%, and oocyst density by 66.3 and 63.3%, respectively. Genetic knockout of the psop25 gene did not have a detectable impact on the asexual growth of P. berghei, but significantly affected the maturation of ookinetes and the formation of midgut oocysts.ConclusionsThe full-length rPSOP25 could elicit strong antibody response in mice. Polyclonal and monoclonal antibodies against PSOP25 could effectively block the formation of ookinetes in vitro and transmission of the parasites to mosquitoes. Genetic manipulation study indicated that PSOP25 is required for ookinete maturation in P. berghei. These results support further testing of the PSOP25 orthologs in human malaria parasites as promising TBV candidates.
Highlights
Plasmodium ookinete surface proteins as post-fertilization target antigens are potential malaria transmission-blocking vaccine (TBV) candidates
The results showed that immunization with recombinant PSOP25 (rPSOP25) induced strong antibody responses as compared to the negative control; the rPSOP25-specific IgG titers increased continuously during the course of vaccination (Student’s t-test: t(10) = 35.13, P < 0.0001; Fig. 1b)
This study confirmed that the full-length recombinant protein of a newly identified TBV candidate Putative secreted ookinete protein 25 (PSOP25) expressed in ookinetes of the rodent parasite P. berghei could elicit a strong antibody response in mice
Summary
Plasmodium ookinete surface proteins as post-fertilization target antigens are potential malaria transmission-blocking vaccine (TBV) candidates. Due to the spread of insecticide-resistant mosquitoes and multidrug-resistant parasites, major malaria control efforts including vector control and chemotherapy are becoming increasingly ineffective [2,3,4]. These trends highlight the need for developing an integrated malaria control strategy to eliminate malaria transmission. A transmission-blocking vaccine (TBV) targeting the sexual stages of the Plasmodium has the potential to reduce malaria transmission and prevent the spread of resistant parasites. Mathematical models further predict that TBVs will be an effective tool for malaria elimination [7]
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