Advancing Malaria Prevention: Genetically Modified Parasites as a Next-Generation Vaccine

Sub : Sci

Sec: Biotech

Why in News

Recent advancements in malaria research have highlighted the use of genetically modified parasites as a novel approach to priming the immune system against malaria. A groundbreaking study demonstrated the efficacy of late-arresting genetically modified parasites in providing enhanced protection compared to conventional methods like radiation-attenuated sporozoites.

Background:

Use of genetically modified mosquitoes includes:
- Release of radiation-sterilized males to prevent egg hatching.
- Slowing parasite growth in mosquito guts to prevent transmission.
- Genetically engineering mosquitoes to spread resistance to malaria-causing parasites.

Genetic Modification of Parasites:

Parasites are genetically modified to not cause disease.
These modified parasites prime the immune system during their liver-stage life cycle before entering the
Priming the immune system shields individuals when subsequently bitten by infected mosquitoes.

Aspect	Radiation-Attenuated Sporozoites	Genetically Modified Parasites
Method of Action	Sporozoites are weakened using radiation, preventing them from causing disease.	Parasites are genetically modified to arrest their growth in the liver.
Stage of Arrest	Parasite life cycle is disrupted immediately upon entering the liver.	Parasites are arrested on day six of the liver stage (late-arresting).
Immune Priming	Shorter exposure period limits immune priming.	Longer exposure period allows more effective immune priming.
Efficacy	Protection levels vary (50–90%) depending on dosage.	Late-arresting parasites show ~89% protection in trials.
Dose Requirement	Requires approximately 1,000 mosquito bites for sufficient exposure.	Requires only 50 mosquito bites per immunization session.
Cellular Immunity	Limited role in inducing specific T-cell responses.	Late-stage antigens induce strong P. falciparum-specific T-cell responses.
Challenges	Logistical difficulty in administering large doses of sporozoites.	Safety and long-term durability of immunity need further research.

About Malaria:

A mosquito-borne disease caused by Plasmodium parasites, primarily transmitted by female Anopheles mosquitoes.
Five species infect humans: P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi.
Symptoms: Fever, chills, headache, muscle pain, and severe cases can lead to complications like cerebral malaria and death.
Endemic in tropical and subtropical regions, with Africa bearing the highest burden.

About Plasmodium falciparum:

The most virulent malaria-causing parasite, responsible for most malaria-related deaths globally.
Capable of rapid multiplication in the bloodstream, leading to severe anaemia and cerebral malaria.
Transmission: Sporozoites from mosquito saliva infect the human liver, then multiply and invade red blood cells.

About T Cells:

A type of white blood cell critical in adaptive immunity, identifying and killing infected cells or activating other immune responses.
Types: Includes helper T cells (CD4+) and cytotoxic T cells (CD8+).
T cells respond to malaria antigens during the liver and blood stages, contributing to immune defence.

About Gamma Delta T Cells: A subset of T cells involved in recognizing and responding to non-protein antigens.

They play a role in immunity against liver-stage malaria parasites, particularly in experimental late-arresting parasite trials.

About Sporozoites:

The infectious stage of Plasmodium parasites transmitted by mosquito bites.
Enter the bloodstream and travel to the liver, where they mature into merozoites.