27 Devastating Infectious Diseases
This Malaria Vaccine Is Delivered By A Mosquito Bite
Some mosquitoes carry the parasite Plasmodium falciparum, which transmits malaria.Credit: CDC/SPL
Scientists have developed a new vaccination strategy for malaria — boosting immunity through bites from mosquitoes carrying a genetically engineered version of the parasite that causes malaria. In a trial, the approach reduced participants' susceptibility to malaria, potentially paving the way for more effective ways to stop the disease, which infects some 250 million people a year.
"These findings represent a significant step forward in malaria vaccine development," says Julius Hafalla, an immunologist at the London School of Hygiene & Tropical Medicine. "The ongoing global malaria burden makes the development of more effective vaccines a critical priority."
The study, which was published1 in The New England Journal of Medicine on 20 November, exposed participants to bites from mosquitoes that had a modified version of the Plasmodium falciparum parasite, which causes malaria. In humans, the parasites travel to the liver and then infect red blood cells. The parasites were engineered to stop developing shortly after delivery into a human. Nearly 90% of participants exposed to the modified parasites avoided contracting the disease after being bitten by malaria mosquitoes.
There are two approved malaria vaccines. Both aim to provide long-term immunity by producing antibodies that block malaria parasites from infecting liver cells, as well as targeting breakthrough infections.
But the vaccines are only about 75% effective, and require booster shots. So immunologists are continuing to explore alternative strategies.
One approach is using genetically modified parasites. The research team had previously trialled the effectiveness of a modified malaria parasite, called GA1, that is designed to stop developing about 24 hours after infection in humans2. But the GA1 parasite protected only a few participants against malaria, leading the team to engineer a second parasite, GA2. GA2 is designed to stop developing about six days post-infection, during the crucial period where the parasites replicate in human liver cells.
The researchers tested whether exposure to GA1 or GA2 could help humans develop immunity to malaria. They exposed participants to bites from 50 mosquitoes; 10 participants received bites from mosquitoes infected with GA1 parasites, and 10 were bitten by those with GA2 parasites. Three weeks later, they exposed participants to malaria-carrying mosquitoes. Just before exposure to these mosquitoes, both sets of participants had higher levels of antibodies than before. One of eight (13%) participants bitten by GA1 parasites didn't contract malaria compared with 89% in the GA2 group. Other than the the itching associated with mosquito bites, side effects were limited.
The researchers are now keen to replicate their results in a larger trial.
The work "should be followed by more extensive studies to confirm GA2's viability as a candidate for global malaria control", says Hafalla.
Antibody Discovery Improves Malaria Treatment
Malaria is a life-threatening disease that is transferred by mosquito bites. Interestingly, a specific type of mosquito can carry the disease. The transfer of the parasite to humans travels to the liver where it can lie dormant for weeks before infecting red blood cells. Once the infection spreads to the blood, patients start having symptoms including fever, headache, chills, fatigue, vomiting, nausea, body aches, and yellow skin. At this point a mosquito can bite that infected person and further transmit the disease.
Healthcare professionals consider malaria a medical emergency that require immediate attention. Chloroquine is a common treatment given to malaria patients, but many others are available for those that are chloroquine resistant. Malaria is most common in Africa, but can also occur in Central and South America, as well as Southeast Asia. To prevent malaria, individuals take precautions to avoid mosquito bite risk. Therefore, mosquito nets and repellent help reduce risk. Individuals can also wear protective clothing and use vaporizers.
In addition to mosquito control strategies, scientists are developing vaccines and other drug treatments to more effectively treat malaria. This is particularly important for malaria strains that are drug-resistant. Unfortunately, the biological mechanism of malaria is still not completely understood, and scientists are working to learn more about this parasite to provide enhanced treatments.
A recent paper in Nature, by Dr. Thomas Lavstsen and others, discovered antibodies that can recognize, and target proteins associated with malaria. This is a major breakthrough in the field of malaria treatment. Specifically, this paves the way for improved malaria vaccines and anti-malaria drugs. Lavsten is a professor within the Department of Immunology and Microbiology at the University of Copenhagen. His work focuses on malaria life cycle, progression, and malaria vaccine development. His recent work focuses on malaria's interaction with the immune system and how our body responds to treatments.
Progressive or severe malaria is caused by a parasite known as Plasmodium falciparum, which infects red blood cells. As a result, the red blood cells stick to blood vessels and cause disruption of blood flow. Clogged blood vessels can lead to fatal injury, especially if it occurs in the brain. The blocked vessels are caused by a family of malaria-related proteins which allow the red blood cells to stick to the blood vessel walls. Researchers wanted to understand ways to target these surface proteins to eliminate blood vessel obstruction. In collaboration with other research groups, Lavsten and his team found an antibody that targets these proteins and avoids the development of blood vessel clotting.
The team developed a technique to grow human blood vessels in a dish and used this to test whether the antibody had an effect on malaria infected blood. The team could not use mouse models because mouse biology against malaria is too different and would not have translated well to humans. Therefore, researchers treated malaria-infected blood with the suspected antibody and found a significant decrease in blood vessel occlusion.
Lavsten and others for the first time discovered an antibody that can target a wide array of malaria surface proteins to avoid blood clots. This discovery has major implications on the development of malaria vaccines and has the potential to reduce risk in children who have low levels of these specific antibodies. Overall, this research has the potential to improve current malaria treatment and increase patient survival.
Paper, Nature, Thomas Lavstsen, University of Copenhagen
Malaria And The Liver: Exploring The Silent Pathway
Cite this articleO'Connell, D. Malaria and the liver: exploring the silent pathway. Nat Rev Microbiol 5, 909 (2007). Https://doi.Org/10.1038/nrmicro1809
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