Pfs230 Domains 7-10 Encoded by DNA Vaccines Induce Potent Complement-Independent Transmission-Blocking Antibody...

Malaria transmission-blocking vaccines (TBVs) targeting parasite transmission by mosquitoes represent a valuable public health tool for malaria control and elimination through herd immunity in the 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.

DNA vaccines encoding Pfs230 domains D7 to D10 (D7D10) were developed and evaluated in BALB/c mice. Antigen-specific antibody responses were assessed via enzyme-linked immunosorbent assay. Transmission-reducing activity (TRA) of antibodies induced by D7D10 DNA and protein vaccines were evaluated in standard membrane feeding assays (SMFAs) using in vitro-cultured P falciparum gametocytes. In addition, we investigated functional activity of antibodies induced by DNA vaccines encoding smaller subdomains D7 and D7D8.

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-D12) suggested that antibodies elicited by D7D10 vaccines predominantly target D7. Furthermore, DNA vaccines encoding D7 and D7D8 similarly induced antibodies with strong TRA in SMFAs.

Our studies identify Pfs230-D7D10, particularly D7, as a novel and promising P falciparum TBV candidate.