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First Cryo-EM Map of Malaria Fertilization Complex Enables mRNA Vaccine Blocking 99.7% of Transmission

Identification of a previously unknown region vital to parasite reproduction has guided an mRNA vaccine strategy now preparing for clinical trials.

An Anopheles stephensi mosquito – which is known to carry malaria – seen obtaining a blood meal from a human host through its pointed proboscis
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Overview

  • Researchers at WEHI published in Science the first cryo-electron microscopy structure of the endogenous Pfs230–Pfs48/45 fertilization complex of Plasmodium falciparum.
  • The structure revealed a new functional region essential for parasite fertilization and reproduction inside mosquitoes.
  • Using these insights, the team collaborated with Monash’s mRNA Core facility to design a vaccine that elicited high antibody levels against the parasite.
  • In preclinical trials, the mRNA candidate achieved a 99.7% reduction in parasite transmission to mosquitoes by targeting critical protein contact points.
  • The vaccine is slated for clinical development and is envisioned as part of a multi-stage malaria eradication strategy alongside blood- and liver-stage vaccines.