The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro

Abstract

Anti-malarial transmission-blocking vaccines (TBVs) aim to inhibit the transmission of Plasmodium from humans to mosquitoes by targeting the sexual/ookinete stages of the parasite. Successful use of such interventions will subsequently result in reduced cases of malarial infection within a human population, leading to local elimination. There are currently only five lead TBV candidates under examination. There is a consequent need to identify novel antigens to allow the formulation of new potent TBVs. Here we describe the design and evaluation of a potential TBV (BDES-PbPSOP12) targeting Plasmodium berghei PSOP12 based on the baculovirus dual expression system (BDES), enabling expression of antigens on the surface of viral particles and within infected mammalian cells. In silico studies have previously suggested that PSOP12 (Putative Secreted Ookinete Protein 12) is expressed within the sexual stages of the parasite (gametocytes, gametes and ookinetes), and is a member of the previously characterized 6-Cys family of plasmodial proteins. We demonstrate that PSOP12 is expressed within the sexual/ookinete forms of the parasite, and that sera obtained from mice immunized with BDES-PbPSOP12 can recognize the surface of the male and female gametes, and the ookinete stages of the parasite. Immunization of mice with BDES-PbPSOP12 confers modest but significant transmission-blocking activity in vivo by active immunization (53.1% reduction in oocyst intensity, 10.9% reduction in oocyst prevalence). Further assessment of transmission-blocking potency ex vivo shows a dose-dependent response, with up to a 76.4% reduction in intensity and a 47.2% reduction in prevalence observed. Our data indicates that PSOP12 in Plasmodium spp. could be a potential new TBV target candidate, and that further experimentation to examine the protein within human malaria parasites would be logical.

Comparative Proteomics and Functional Analysis Reveal a Role of Plasmodium falciparum Osmiophilic Bodies in Malaria Parasite Transmission

“…This is surprising as this protein was independently identified in both the global comparative proteomics and the co-IP approaches. Moreover, similar to other OBC proteins identified in this study, the ortholog of this protein in the murine parasite P. berghei, PbPSOP12, has been detected on the gametocyte surface (39). Therefore, failure to detect PfPSOP12 in OBs could be an artifact of incorrect trafficking of the chimeric GFP-tagged fusion protein and further experiments using anti PfPSOP12 antibodies are needed to clarify this discrepancy.…”

Functional characterization of Plasmodium berghei PSOP25 during ookinete development and as a malaria transmission-blocking vaccine candidate

“…However, there was a greater degree of reduction in oocyst prevalence in mosquitoes fed on mice immunized with the full-length protein (31.2%) as compared to that in mosquitoes fed on mice immunized with the partial rPSOP25 (25%) [26]. The TB activities of PSOP25 were comparable to those of PSOP12 [44], PSOP7 and PSOP26 [26] in the reduction of oocyst density and infection prevalence in DFA. Furthermore, monoclonal antibodies have been a valuable tool for the characterization of TBVs [45, 46].…”

The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle

“…Mass spectrometry data indicates it is expressed in gametocytes, ookinetes and oocyts in P. berghei and in P. falciparum (Florens et al, 2002; Hall et al, 2005; Ecker et al, 2008; Silvestrini et al, 2010). Live and immunofluorescence microscopy of PSOP12-GFPtagged parasites detected the protein on the surface of male and female gametocytes, gametes and ookinetes (Sala et al, 2015). Plasmodium berghei ΔPSOP12 parasites showed only a mild, non-significant reduction in oocyst production, resulting in normal numbers of sporozoites and normal transmission to mice (Ecker et al, 2008).…”

“…Plasmodium berghei ΔPSOP12 parasites showed only a mild, non-significant reduction in oocyst production, resulting in normal numbers of sporozoites and normal transmission to mice (Ecker et al, 2008). Nevertheless, a recent vaccine study using baculovirus-expressed PbPSOP12 reported a small but significant transmission-blocking activity for antibodies to this protein both in vitro and in mice (Sala et al, 2015). Further characterization of SOP12 in P. falciparum and P. yoelii is required to determine whether robust blocking transmission activity can be achieved by targeting this protein.…”