genetically modified mosquitoes to vaccinate on a large scale?

THE ESSENTIAL

  • Malaria is generally characterized by high fever, cough, muscle aches, headaches, vomiting and diarrhoea.
  • Different species of parasites can cause malaria in humans. We distinguish in particular: Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax or Plasmodium knowlesi.

Each year, nearly 5,500 people are affected by malaria in France. This infectious disease is caused by several species of parasites belonging to the genus Plasmodium. Transmission occurs through the bite of a female mosquito infected with the parasite that causes malaria. The main species carrying the disease is l’Anopheles gambiae.

The parasites (Plasmodium falciparum) travel to the liver to multiply when a malaria-infected mosquito bites an individual. The liver stage is asymptomatic, but symptoms occur when the parasites spread and contaminate red blood cells.

Red blood cells contaminated with malaria can clog the blood vessels responsible for supplying blood to the brain. Cerebral malaria, a complication manifested by high fever and convulsions, can then occur. This severe form of malaria can lead to coma.

A vaccine to prevent the parasite from reproducing in the liver

A team from the Seattle Children’s Research Institute and the National Institutes of Health (USA) recently developed an early version of a vaccine called PfGAP3KO. To achieve this, they genetically modified the parasites responsible for malaria in mosquitoes carrying the disease.

The scientists used the CRISPR system, which allows DNA to be cut at a specific location in the genome in any cell. The researchers therefore made three deletions, in other words losses of DNA fragments, in the genes P52, P36 and SAP1 parasites. These three “cuts” prevented them from replicating in the liver and reaching red blood cells. Their work has been published in the journal Science Transnational Medicine.

Individuals exposed to the bites of malaria-carrying mosquitoes

For the purposes of the study, 26 participants were recruited and vaccinated by mosquitoes infected with genetically modified parasites. During the research, volunteers received their dose of vaccine by placing one arm below a mesh-covered container filled with mosquitoes. This immunization phase was repeated three to five times.

The scientists then exposed 14 of the 26 participants to mosquitoes contaminated with unmodified malaria parasites. Nearly 50% of the volunteers did not develop a blood-stage infection. Six months later, a few subjects were reintroduced to malaria-infected mosquitoes. They all remained partially protected against infection.

A vaccine offering a better immune response

For the time being, there is only one vaccine against malaria which is still at the experimental stage: the “RTS,S”. Since 2021, the World Health Organization (WHO) recommends its use for children living in areas with moderate to high malaria transmission. Plasmodium falciparum

In the eyes of the American researchers, their “live” vaccine offers better protection and immunity than the RTS vaccine, S. “The RTS,S is a subunit vaccine, so the immune system responds to a single antigen, whereas our vaccine (…) expresses thousands of antigens (…) So you will get an immune response to a large number of these antigens”, said Dr. Ashley Vaughan, co-lead author of the study and assistant professor of pediatrics at the University of Washington School of Medicine, in a statement.

The vaccine PfGAP3KO was generally well tolerated by all the volunteers. Only one adverse effect was identified: hives caused by numerous mosquito bites. In the future, the researchers hope to start a clinical trial with an injectable version via syringes of their vaccine.


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