Pfs230 Domains 7–10 Encoded by DNA Vaccines Induce Potent Complement-Independent Transmission-Blocking Antibody Against Plasmodium falciparum

Background: Malaria transmission-blocking vaccines (TBV) targeting parasite transmission by mosquitoes represent a valuable public health tool for malaria control and elimination through herd immunity in community. Pfs230, a surface protein expressed in gametocytes and gametes of Plasmodium falciparum, plays a critical role in gamete fertilization and further development within mosquitoes. Prior studies have advanced the N-terminal Pro-domain (Pro) and domain 1 (D1) of Pfs230 as a putative TBV target. However, whether other Pfs230 domains function as TBV candidates needs further study. Methods: DNA vaccines encoding Pfs230 domains D7 to D10 (D7D10) were developed and evaluated in BALB/c mice. Antigen-specific antibody responses were assessed via ELISA. Transmission reducing activity (TRA) of antibodies induced by D7D10 DNA and protein were evaluated in standard membrane feeding assays (SMFA) using in vitro cultured P. falciparum gametocytes. In addition, we investigated functional activity of antibodies induced by DNA vaccines encoding smaller sub-domains D7 and D7D8. Results: Potent D7D10-specific antibody responses were elicited in mice immunized with DNA vaccines. Anti-D7D10 IgGs purified from mice revealed strong dose-dependent TRA against P. falciparum in SMFA, irrespective of the presence or absence of active complement. Western blot analysis using various Pfs230 fragments (D5 to D12) suggested that antibodies elicited by D7D10 vaccines predominantly target domain 7. Furthermore, DNA vaccines encoding D7 and D7D8 similarly induced antibodies with strong TRA in SMFA. Conclusion: Our studies identify Pfs230-D7D10, particularly D7, as a novel and promising P. falciparum TBV candidate.