Australian researchers discover a new goal for new generation malaria vaccines

Australian researchers for the first time hung up a key protein complex in malaria parasites, discovering the new goal of new generation vaccines that could stop the spread of the disease.

With the help of the latest cryroscopy of cryo -electron, the Wehi research syndrome captured the first detailed structure of the protein complex necessary to fertilize malaria parasites.

The published discovery led to the development of a promising new candidate for the MRNA vaccine, which stops the malaria parasite from reproduction inside the mosquitoes, breaking the transmission cycle before it reaches people.

Malaria remains one of the most deadly infectious diseases responsible for over 600,000 deaths a year.

At first glance

• Wehi scientists captured the first high -resolution structure of the key protein complex, which is necessary for the malaria parasite to breed in mosquitoes.
• They discovered two small domains of the PFS230-PFS48/45 fertilization complex, which are crucial for the ability of the parasite to fertilize and spread.
• The new MRNA vaccine antibodies induced those domains that stopped the parasite from reproducing in mosquitoes, crossing the transmission by up to 99.7%.

Visualization of malaria reproduction machines

For many years, scientists know that two key proteins that appear on the surface of the malaria parasite, PFS230 and PFS48/45 are important for the transmission of the disease.

The main researcher Dr. Melanie Dietrich said that the new study for the first time revealed, like the interactions of these proteins – revealing a new vaccine goal.

The key was our approach to structural biology. Using cryroscopy of cryo-electron, we were able to visualize a full fertilization complex directly from the parasite-not the laboratory version.

This gave us a clear picture of how this fertilization complex really looks by nature, and revealed a previously unknown region, which is crucial for this process, unlocking the new vaccine goal. “

Dr. Melanie Dietrich, a doctoral student of Wehs, main researcher

The main researcher Professor WAI-Hong Tham said that by intercepting the fertilization complex directly from the parasite, the team revealed exact contact points that allow transmission.

“We used these arrangements to develop a vaccine, which showed a great promise in directing these contact points,” said prof. Tham, laboratory chief of IHI.

“EliminateWe have to stop the broadcast. This vaccine candidate can be one piece of this puzzle. “

From structural insight to vaccine innovation

Unlike many studies of structural biology, which are based on proteins produced in the laboratory of bacterial cells, insects or mammals, new studies have successfully cleaned the fertilization complex directly from malaria parasites – a technically difficult approach that ensures the structure reflects its true biological form.

The study revealed critical contact points for binding PFS230 and PFS48/45 proteins. When they were removed in genetically modified parasites, the fertilization failed and the transfer was blocked, illuminating the new target of the vaccine.

Based on the structural discovery, the team designed a new generation MRNA vaccine, which was formulated in cooperation with MRNA Core Facility at the Monash Institute of Pharmaceutical Sciences (MIPS).

In pre -clinical studies, the vaccine caused high levels of antibodies that recognized the parasite and blocked transmission in mosquitoes by up to 99.7%.

Professor Colin Pouton from MIPS said that his team is an exciting opportunity to use their specialist knowledge in the development of MRNA vaccines in order to remedy an important new purpose of vaccination in the matter of malaria.

“Based on experience through MRNA Core, the MIPS team focused on a new challenge on vaccinating malaria,” said prof. Pouton.

“The success of the malaria vaccine program is illustrated by the versatility of MRNA technology, which has many applications outside of Covid vaccines. Working on this project with the Wehi team, located in the Parkville district, in which specialist knowledge helped in a new approach to the approach to the approach to the approach to approach was particularly satisfying. Malaria prevention. “

A sensitive stage in the parasite life cycle

Going to the parasite in mosquitoes offers a strategic advantage because of what researchers call a bottleneck.

While malaria parasites are abundant in the human host, only a small faction develops in sexual forms and are effectively fertilized in mosquitoes. This bottleneck means that even a slight reduction in the number of parasites at this stage can have a significant impact on transmission.

Transmission blocking vaccines-like those designed in these studies, focused on the malaria parasite in mosquito-offer a strategic way of retaining malaria, where its number is the lowest and his life cycle is the most sensitive.

Multi -stage elimination strategy

The team predicts the MRNA vaccine as part of a multi -stage strategy, focused on the parasite in both mosquitoes and the human host.

By combining vaccines that block transmission with those that work at the blood or liver stage in humans, scientists hope to build a comprehensive defense, which can radically reduce the painting load and approach the elimination.

Prof. Tham said that the cooperation between Ihi and MIPS emphasized the strength of the biomedical district in Melbourne and the potential of MRNA technology to quickly translate basic learning into vaccine innovation.

“The ability to design, formulate and test candidates for a vaccine in one research ecosystem has accelerated the path from discovering to pre -clinical validation,” she said.