A faster method to collect pure malaria parasites from infected mosquitoes could accelerate the development of new, more potent malaria vaccines.
The new method, developed by a team of researchers led by Imperial College London, allows for the rapid isolation of more parasites with less pollutants, which could both increase the scalability and effectiveness of malaria vaccines.
The malaria-causing parasite is increasingly resistant to antimalarial drugs, with the mosquitoes which transmit the disease also increasingly resistant to pesticides. This has created the urgent need for new ways to fight malaria, which is the third deadliest disease in the world in children under five, with one child dying of malaria every two minutes.
Existing malaria vaccines that use whole parasites offer moderate protection against the disease. In these vaccines, the parasites are “attenuated,” as are some flu vaccines and the MMR vaccine, so they infect people and increase a strong immune response that protects against malaria but does not cause the disease.
However, these vaccines require several doses, and each dose potentially requires tens of thousands of parasites in an early stage of their development, known as sporozoites. Sporozoites are usually found in the salivary glands of mosquitoes and, in a natural infection, are transmitted to humans when mosquitoes bite. They then travel to the human liver, where they prepare to cause infections in the body.
The extraction of sporozoites for use in a live vaccine currently requires manual dissection of the salivary glands of mosquitoes — tiny structures behind the mosquito’s head — by a qualified technician, which involves an expensive and costly process of time.
The new method, described today in the Life Science Alliance, greatly speeds up this process by effectively creating a “mosquito smoothie” and filtering the resulting liquid by size, density, and electrical charge, leaving a pure sporozoite product suitable for vaccination. It is important to note that dissection is not required.
Senior Research Professor Jake Baum, of the Imperial Department of Life Sciences, said: “The creation of vaccines against whole parasites in sufficiently large volumes and in a timely and cost-effective manner has been one of the main obstacles to advancing in malaria vaccination, unless you can employ an army of skilled mosquito dissectors. Our new method presents a way to cheapen, accelerate, and radically improve vaccine production. “
But it’s not just about speed and cost. Traditional dissection methods struggle to remove all contaminants, such as proteins from the salivary glands, which are often extracted with sporozoites. Additional waste is likely to affect the infectivity of sporozoites once inside the body and may even affect the immune system’s response, affecting the effectiveness of any vaccine against the parasite.
The new method also addresses this problem, resulting in pure uncontaminated sporozoite samples. The team found that in addition to being purer, the sporozoites produced were surprisingly more infectious, suggesting that vaccines produced by their method may require a much lower dose of sporozoites.
The study’s lead author, Dr. Joshua Blight of Imperial’s Life Sciences Department, said: “With this new approach we are not only improving the scalability of vaccine production, but our isolated sporozoites. they can prove to be more potent as a vaccine, giving us an extra mosquito blast. “
The team developed and tested their method with both human and rodent malaria parasites. They then tested the rodent version as a vaccine in mice and found that when exposed to an infected mosquito bite, vaccinated mice had 60-70% protection when vaccines were given to the muscle. When the same sporozoites were administered directly into the bloodstream (intravenously), the protection was 100%, known as “sterile” protection.
Researchers are now developing the method to prepare the mass manufacture of sporozoites under good manufacturing practice (GMP) conditions to produce a vaccine prepared for human-challenged trials. The plan is for participants to be given vaccine-grade sporozoites produced by this method and then deliberately bitten by an infected mosquito.
Looking beyond vaccines, researchers also claim that their method should help speed up studies of sporozoite biology in general, which in turn could lead to new knowledge about the liver stage of malaria and new drug i vaccine regimes.
Joshua Blight et al, independent production of Plasmodium sporozoite dissection from whole mosquitoes, Life Science Alliance (2021). DOI: 10.26508 / lsa.202101094
Imperial College London
Citation: “Mosquito Smoothie” Innovation Increases Potential Future Malaria Vaccine (2021, June 17) Retrieved June 17, 2021 at https://medicalxpress.com/news/2021-06-mosquito-smoothie-boosts -future-malaria.html
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