Researchers from Leiden University Medical Center (LUMC) and Radboud University in the Netherlands have successfully engineered mosquitoes to deliver vaccines that could provide enhanced immunity against malaria. The approach involves using genetically modified mosquitoes to administer a weakened strain of the malaria parasite, Plasmodium falciparum.
The World Health Organization estimates that there were 597,000 malaria deaths globally in 2023, with African countries accounting for 95% of these fatalities. Children and pregnant women are particularly vulnerable, with over 240 million cases occurring annually worldwide, highlighting the urgent need for effective malaria prevention strategies.
How the Mosquito-Delivered Vaccine Works
The vaccine employs a weakened strain of Plasmodium falciparum, the parasite responsible for the deadliest form of malaria in humans. According to vaccinologist Meta Roestenberg, the modified parasite still infects people but does not cause illness because a crucial gene has been removed. The mosquito-delivered vaccine mirrors the natural transmission of malaria, aiming to create a strong immune response in the liver, thus protecting against infection.
Normally, malaria parasites are transferred to humans through mosquito bites. The mosquito's proboscis pierces the skin, injecting saliva containing parasites into the bloodstream. These parasites then travel to the liver, reproduce rapidly, and infect red blood cells, leading to malaria symptoms like fever and chills. The modified parasite in the vaccine cannot complete its development in the liver, preventing it from entering the bloodstream and causing disease.
Clinical Trial Results
In a clinical trial, participants received mosquito-delivered versions of two vaccines: GA1 and GA2. The GA1 vaccine allowed the parasite to replicate in the liver over 24 hours, while the GA2 vaccine extended this period to a week, providing the immune system more time to recognize and combat the parasite. The trial results, published in the New England Journal of Medicine, indicated that 89% of the GA2-infected group developed immunity to malaria, compared to 13% in the GA1-infected group and none in the placebo group.
Previous Research
Prior to this, an injectable malaria vaccine derived from a genetically modified parasite known as PfSPZ GA1 was tested. The study, published in Science Translational Medicine, showed the GA1 vaccine was safe but only delayed the onset of malaria without preventing the disease entirely. In 2022, a study in Seattle explored mosquitoes as vaccinators using CRISPR gene-editing technology to weaken malaria-causing Plasmodium parasites, achieving 50% effectiveness.
Future Directions
Despite the promising results, the GA2 vaccine requires further testing in larger studies to determine its long-term efficacy and its ability to protect against different strains of the malaria parasite. Roestenberg noted that while using mosquitoes as vectors is a quicker way to deliver malaria sporozoites, it is not sustainable in the long term. The ultimate goal is to develop a vialed vaccine for widespread use in Africa.
Roestenberg emphasized that mosquitoes could not be implemented to deliver immunizations on a large scale and that this approach is only feasible in the context of a clinical trial.
