Scientists Unveil Malaria Vaccine Blocking Mosquito Transmission
Breakthrough targets parasite’s reproductive cycle
Australian researchers have achieved a significant milestone in the fight against malaria, a disease claiming over 600,000 lives annually. For the first time, they have visualized a critical protein complex of the malaria parasite, paving the way for a novel mRNA vaccine designed to halt transmission between mosquitoes and humans.
Visualizing the Parasite’s Reproductive Machinery
A team at the Walter and Eliza Hall Institute (WEHI) has successfully mapped the structure of a protein complex essential for malaria parasite fertilization within mosquitoes. This groundbreaking achievement, utilizing advanced cryo-electron microscopy, revealed previously unknown interaction points crucial for parasite reproduction.
Dr. Melanie Dietrich, a lead researcher at WEHI, explained the significance of their approach: Our structural biology approach was the key. Using cryo-electron microscopy, we were able to visualise the full fertilisation complex directly from the parasite – not a lab-made version.
She added, This gave us a clear picture of how this fertilisation complex really looks in nature and revealed a previously unknown region that’s crucial to the process, unlocking a powerful new vaccine target.
From Molecular Insight to mRNA Vaccine
The WEHI study focused on two key surface proteins, Pfs230 and Pfs48/45, known to be vital for parasite transmission. By purifying the fertilization complex directly from the parasite, the researchers obtained an accurate representation of its natural form, a technically demanding feat.
Identifying specific binding sites between Pfs230 and Pfs48/45 allowed the scientists to engineer genetically modified parasites with these sites removed. This modification effectively prevented fertilization and blocked transmission, confirming these contact points as prime vaccine targets.
Collaborating with the Monash Institute of Pharmaceutical Sciences (MIPS), the team developed a next-generation mRNA vaccine. Preclinical trials demonstrated that this vaccine elicited robust antibody responses capable of recognizing the parasite and achieving up to a 99.7 percent blockage of transmission in mosquitoes.
Professor Colin Pouton from MIPS highlighted the collaborative success: Drawing on experience through mRNA Core, the MIPS team shifted focus to tackle a new challenge in malaria vaccination. The success of the malaria vaccine program illustrates the versatility of mRNA technology, which has many applications beyond the COVID vaccines.
He further commented, It was particularly rewarding to work on this project with the WEHI team, co-located in the Parkville precinct, where shared expertise has helped drive a new approach to malaria prevention.
Targeting a Vulnerable Stage
The vaccine targets the malaria parasite during a critical “population bottleneck” within the mosquito, where only a fraction of the parasites successfully develop into sexual forms capable of fertilization. This strategic targeting of the parasite at its most vulnerable stage significantly enhances the potential for transmission control.
A Multi-Stage Strategy for Malaria Elimination
This transmission-blocking mRNA vaccine is envisioned as part of a comprehensive, multi-stage strategy. Experts believe that combining this approach with vaccines targeting the parasite’s blood and liver stages in humans could establish a robust defence, greatly reducing the burden of malaria and accelerating eradication efforts.
The ability to rapidly advance from discovery to preclinical validation, as demonstrated by this project, offers hope for accelerated progress against this devastating disease. In 2023, malaria affected an estimated 249 million people worldwide, underscoring the urgent need for innovative control measures (WHO, 2024).
