RTS,S Malaria Vaccine (brand name, Mosquirix): The First Approved Malaria Vaccine
Works on liver stage - before parasite emerges into blood
Passed phase III - now in pilot implementation in selected African countries (Ghana, Malawi, Kenya)
Reduces severe malaria by 31.5% (WHO data)
Efficacy is lost if only 3 doses are taken
Efficacy wanes quickly, booster required
4th dose recommended after 18 months
Who is this vaccine for?
- Young children (5–17 months old)
Who is this vaccine not for?
Newborns (<6 weeks old) – Excluded due to potential interference with maternal antibodies and early immune system immaturity.
Older children (>17 months) – While some earlier studies included children up to 4–5 years old, the main trials focused on younger age groups where malaria burden is highest.
Adolescents & Adults – RTS,S was designed primarily for childhood malaria prevention, as adults in endemic areas develop partial immunity over time.
Which P. falciparum Protein Does the Vaccine Target
Malaria vaccines primarily target proteins involved in infection, immune evasion, and parasite development. These proteins are found in different stages of the parasite's life cycle.
RTS,S (a recombinant protein vaccine) targets the circumsporozoite protein (CSP) of P. falciparum.
What is the Purpose of the Circumsporozoite Protein
This protein is found on the surface of sporozoites. Sporozoites are the form of the parasite that a mosquito injects into a human.
The protein is essential for the parasite's ability to invade liver cells.
Vaccines targeting this stage aim to stop the parasite before it infects red blood cells.
Incidentally, the R21/Matrix-M vaccine also targets this protein.
Additional Sporozoite Protein Targeted by a Vaccine
Another parasite protein to note is the Thrombospondin-Related Adhesive Protein (TRAP). This protein is involved in sporozoite motility and liver cell invasion. A vaccine candidate (ChAd63-MVA ME-TRAP) exists for this protein .
Other Parasite Stages and their vaccine targets (In trial)
Part of the life cycle of P. falciparum involves its emergence from the liver to infect red blood cells (RBCs). At this stage, it expresses several proteins to allow its survival. Some of these proteins include Apical Membrane Antigen 1 (AMA1), Merozoite Surface Proteins (MSP-1, MSP-2, MSP-3) and Reticulocyte-Binding Protein Homologue 5 (PfRH5)
Apical Membrane Antigen 1 (AMA1)
Critical for merozoite invasion into red blood cells.
The vaccine candidate for this is an AMA1-based subunit vaccine.
Merozoite Surface Proteins (MSP-1, MSP-2, MSP-3)
Involved in red blood cell invasion.
There are vaccine candidates that are MSP-based vaccines.
Reticulocyte-Binding Protein Homologue 5 (PfRH5)
Essential for red blood cell invasion via interaction with basigin.
There are vaccine candidates that are RH5-based.
Vaccines Targeting Mosquito Stages of the Parasite
There are additional stages of the parasite development that happens in a mosquito. There are vaccine candidates that target some of these proteins.
These approaches are aimed at transmission-blocking or preventing the spread of malaria. Such vaccines target proteins required for parasite development in the mosquitoes, reducing transmission.
Transmission-Blocking Vaccines
Pfs25 – found on the surface of Plasmodium gametes in the mosquito midgut.
Pfs230 & Pfs48/45 – involved in gamete fertility and fusion inside the mosquito.
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