Abstract
BackgroundTransmission-blocking vaccines (TBVs) are a promising strategy for malaria control and elimination. However, candidate TBV antigens are currently limited, highlighting the urgency of identifying new antigens for TBV development.MethodsUsing a combination of bioinformatic analysis and functional studies in the rodent malaria model Plasmodium berghei, we identified a conserved Plasmodium protein PbPH (PBANKA_041720) containing a pleckstrin homology (PH) domain. The expression of PbPH was detected by Western blot and indirect immunofluorescence assay (IFA). The function of PbPH was tested by genetic knockout. The TB activity was confirmed by in vitro ookinete conversion assay and mosquito feeding.ResultsPbPH was detected in Western blot as highly expressed in sexual stages (gametocytes and ookinetes). IFA revealed localizations of PbPH on the surface of gametes, zygotes, and ookinetes. Deletion of the pbph gene did not affect asexual growth, but significantly reduced the formation of gametocytes, ookinetes, and oocysts, indicating that PbPH protein is required for parasite sexual development. Recombinant PbPH expressed and purified from bacteria elicited strong antibody responses in mice and the antibodies significantly inhibited exflagellation of male gametocytes and formation of ookinetes in a concentration-dependent manner. Mosquito feeding experiments confirmed that mosquitoes fed on mice immunized with PbPH had 13 % reduction in the prevalence of infection and almost 48 % reduction in oocyst density.ConclusionsPbph is a highly conserved Plasmodium gene and is required for parasite sexual development. PbPH protein is expressed on the surface of gametes and ookinetes. Immunization of mice against the recombinant PbPH protein induced strong antibody responses that effectively reduced the formation of male gametes and ookinetes in vitro and blocked transmission of the parasites to mosquitoes. These results highlight PbPH as a potential TBV candidate that is worth future investigations in human malaria parasites.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1459-8) contains supplementary material, which is available to authorized users.
Highlights
Transmission-blocking vaccines (TBVs) are a promising strategy for malaria control and elimination
PbPH is highly conserved among Plasmodium species Through bioinformatic analysis using criteria of protein expression in sexual stages and the presence of a putative signal peptide, we identified a P. berghei gene PBANKA_041720 from the Plasmodium database
In this study, we showed that pbph is a highly conserved Plasmodium gene and PbPH protein localized it on the surface of gametes, zygotes, retorts and ookinetes
Summary
Transmission-blocking vaccines (TBVs) are a promising strategy for malaria control and elimination. Transmission-blocking vaccines (TBVs) targeting sexual and/or sporogonic development of the parasite and designed to prevent malaria transmission in endemic regions are a potentially highly effective strategy especially during malaria elimination [3]. The fundamental principle of TBVs is immunization of humans with surface antigens of sexual- and mosquito-stage parasites to produce antibodies that arrest subsequent development of the parasite in the mosquito midgut, cutting off the transmission of malaria parasites [4]. Antibodies against the male gamete antigen P48/45 are found in human sera from endemic areas and correlate with transmission blocking (TB) activities [11]. Most of the existing TBV candidates have been found to be suboptimal [13], and there is a real need for TBV antigen discovery
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
