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Malaria vaccines

Malaria vaccines are a crucial development in the fight against malaria, a disease caused by parasites transmitted through the bites of infected mosquitoes.

The most notable malaria vaccine is RTS,S/AS01 (brand name Mosquirix), is endorsed by the World Health Organization (WHO) for use in children in areas with moderate to high malaria transmission.

RTS,S/AS01 (Mosquirix)** is approved for use in several African countries.

It targets the Plasmodium falciparum parasite, which is the most dangerous of the malaria parasites.

The vaccine can significantly reduce malaria cases and severe malaria in young children.

Other malaria vaccines are currently in various stages of research and development, including:

– R21/Matrix-M, which has shown promising results in trials and has received attention for its efficacy. -Whole parasite and mRNA vaccine candidates.

Vaccine efficacy may wane over time, and requires booster doses.

Complementary measures, such as insecticide-treated bed nets, indoor spraying, and antimalarial medications, remain essential for controlling malaria transmission.

Malaria, a mosquito-borne infectious disease which affected an estimated 249 million people globally in 85 malaria endemic countries and areas and caused 608,000 deaths in 2022.

The first approved vaccine for malaria is RTS,S, known by the brand name Mosquirix.

It requires at least three doses in infants by age 2, and a fourth dose extends the protection for another 1–2 years.

The vaccine reduces hospital admissions from severe malaria by around 30%.

Routes of administration -Intramuscular

The most effective malaria vaccine is the R21/Matrix-M, with a 77% efficacy rate shown in initial trials and significantly higher antibody levels than with the RTS,S vaccine.

It is the first vaccine that meets with at least 75% efficacy

RTS,S/AS01 (Mosquirix) is the first malaria vaccine approved for public use.

It requires at least three doses in infants by age 2, with a fourth dose extending the protection for another 1–2 years.

The vaccine reduces hospital admissions from severe malaria by around 30%.

It is a recombinant vaccine, consisting of the Plasmodium falciparum circumsporozoite protein (CSP) from the pre-erythrocytic stage.

The CSP antigen causes the production of antibodies capable of preventing the invasion of hepatocytes and also elicits a cellular response enabling the destruction of infected hepatocytes.

A Phase III trial of RTS,S found that it provided modest protection against both clinical and severe malaria in young infants, reducing the number of cases among young children by almost 50 percent and among infants by around 25 percent.

After four years, reductions were 36 percent for children who received three shots and a booster dose.

Missing the booster dose reduced the efficacy against severe malaria to a negligible effect.

The vaccine is less effective for infants.

Three doses of vaccine plus a booster reduced the risk of clinical episodes by 26 percent over three years but offered no significant protection against severe malaria.

The immunity induced consists of an antibody response (humoral immunity) and a cell-mediated immune response.

A vaccine would enable the development of anti-plasmodial antibodies in addition to generating an elevated cell-mediated response.

Antibodies exert their effect by activating the complement cascade, stimulating phagocytic cells into endocytosis through adhesion to an external surface of the antigenic substances, thus ‘marking’ it as offensive.

Humoral or cell-mediated immunity aims to prevent infection entering the body and then kill any micro-organisms or foreign particles that succeed in penetration.

The cell-mediated component consists of many white blood cells: monocytes, neutrophils, macrophages, lymphocytes, basophils, mast cells, natural killer cells, and eosinophils that target foreign bodies by a variety of different mechanisms.

In the case of malaria, both systems would be targeted to attempt to increase the potential response generated, thus ensuring the maximum chance of preventing disease.

Anti-toxic immunity refers to the suppression of the immune response associated with the production of factors that either induce symptoms or reduce the effect that any toxic by-products have on the development of disease.

Tumor necrosis factor-alpha has a central role in generating the symptoms experienced in severe P. falciparum malaria.

The majority of research into malarial vaccines has focused on the Plasmodium falciparum strain due to the high mortality caused by the parasite.

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