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Pfs25 is a leading TBV candidate expressed during the sexual stages of the parasite lifecycle and plays a role in ookinete survival in the mosquito midgut as well as traversal through the midgut epithelium. Pfs25 has progressed through extensive clinical investigation to assess its safety and efficacy. Several approaches have been explored to increase the immunogenicity of Pfs25, including virus-like particle (VLP) display, nanoparticle display, conjugation to Pseudomonas aeruginosa Exoprotein A (EPA) and formulation in diverse adjuvants.
Pfs28 is a glycosylphosphatidylinositol-anchored protein expressed on the surface of zygotes and ookinetes and plays a similar role as Pfs25 in ookinete survival and traversal through the midgut. This function of Pfs28 may be mediated through its interactions with basal lamina proteins surrounding the mosquito midgut. Pfs28 and Pfs25 are thought to play partially redundant roles in parasite survival within the mosquito.