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Malaria and Genetically Modified Malaria Parasites
Context:
Efforts to combat malaria are evolving, with innovative approaches complementing existing strategies such as vaccines and genetically modified mosquitoes.
More on News:
- One of the latest developments involves genetically altering malaria-causing parasites themselves to prevent the disease and prime the immune system, offering hope for a next-generation malaria vaccine.
Moving Beyond Mosquito Modification:
- Older Approaches: Historically, scientists have focused on modifying mosquitoes to curb malaria transmission.
- Methods include releasing sterilised males to prevent reproduction, engineering mosquitoes to hinder parasite growth in their gut, and creating mosquitoes that pass on resistance to malaria-causing parasites when mating with wild populations.
- New Strategy: The new strategy shifts attention to the malaria-causing parasite, Plasmodium falciparum.
- Researchers have genetically modified these parasites to render them harmless while enabling them to stimulate the immune system during their liver-stage lifecycle, well before they enter the bloodstream—the stage where symptoms emerge.
Late-Arresting Parasites:
- The genetic modification stops parasite growth on the sixth day of the liver stage.
- This delay gives the parasites enough time to prime the immune system effectively, providing protection against future malaria infections when bitten by infected mosquitoes.
- In contrast, early-arresting parasites, which are killed on day one in the liver, have a limited window to stimulate the immune system, resulting in less effective protection.
Small-Scale Clinical Trial:
- In a groundbreaking study published in the New England Journal of Medicine, researchers tested the effectiveness of genetically modified parasites in a trial involving 20 healthy adults with no prior exposure to malaria.
- Participants were divided into three groups:
- Late-Arresting Parasite Group: Nine participants exposed to mosquitoes carrying parasites that die on day six.
- Early-Arresting Parasite Group: Eight participants exposed to mosquitoes carrying parasites that die on day one.
- Placebo Group: Three participants bitten by uninfected mosquitoes.
- Each participant underwent three immunisation sessions, each involving 50 mosquito bites and spaced 28 days apart.
- Three weeks after the final session, all participants were exposed to malaria through five bites from mosquitoes carrying unmodified P. falciparum parasites.
Promising Results:
- 89% of the late-arresting group (8 of 9) were protected from malaria.
- 13% of the early-arresting group (1 of 8) were protected.
- None of the placebo group were protected.
- Although both intervention groups showed high antibody levels against P. falciparum antigens, only the late-arresting group displayed specific T-cell responses associated with enhanced protection.
- This suggests the importance of late-liver-stage antigens in inducing immunity.
Advantages Over Radiation-Attenuated Sporozoites:
- Sporozoites, the infectious stage of malaria parasites, have previously been attenuated using radiation to offer protection.
- However, this method requires significantly higher doses—approximately 1,000 mosquito bites—to achieve comparable levels of protection (50–90%).
- Genetically modified late-arresting parasites provide an alternative with improved efficacy at lower doses.
Future Prospects:
- The study marks a significant step toward developing a next-generation malaria vaccine, though the findings are tempered by the trial’s small sample size.
- Researchers stress the need for larger studies to better understand the safety, efficacy, and durability of the protection provided by late-arresting parasites.
- They also emphasise assessing the vaccine’s performance in regions where malaria is endemic, especially against diverse P. falciparum strains.
