Malaria remains a substantial global health challenge, particularly in tropical and subtropical regions where nearly half of the world’s population is at risk. This parasitic disease, transmitted by infected female Anopheles mosquitoes, caused an estimated 263 million cases and 597,000 deaths in 2023. Children under five years of age are disproportionately affected, accounting for approximately 76% of all malaria deaths in the WHO African Region. The disease places an enormous burden on individuals, families, communities, and national health systems.
The Primary Malaria Vaccine
The primary malaria vaccine recommended for widespread use by the World Health Organization (WHO) is RTS,S/AS01, commonly known by its trade name, Mosquirix. This vaccine is the first and only malaria vaccine to receive a broad recommendation from the WHO. It was developed through a collaboration between GSK, a pharmaceutical company, and the PATH Malaria Vaccine Initiative, with research spanning over three decades.
The development of Mosquirix began in 1987 by scientists at GSK, with early clinical studies in collaboration with the Walter Reed Army Institute of Research. Its journey involved extensive clinical trials, including a Phase 3 trial conducted from 2009 to 2014 across seven African countries, involving over 15,000 infants and young children. The WHO officially recommended RTS,S/AS01 in October 2021 for use in children at risk of malaria caused by Plasmodium falciparum, the deadliest malaria parasite globally and the most prevalent in Africa.
How the Vaccine Works
The RTS,S/AS01 vaccine works by targeting the Plasmodium falciparum parasite during its pre-erythrocytic, or liver, stage. When an infected mosquito bites a person, it injects sporozoites, the infectious form of the parasite, into the bloodstream. These sporozoites then travel to the liver cells, where they multiply.
The vaccine contains a recombinant protein that includes parts of the Plasmodium falciparum circumsporozoite protein (CSP) combined with the hepatitis B surface antigen. This composition stimulates the immune system to produce antibodies specifically against the circumsporozoite protein. These antibodies neutralize the sporozoites, preventing them from infecting liver cells or reducing the number of parasites that emerge from the liver, thereby interrupting the parasite’s life cycle before it can cause disease symptoms in the blood.
Vaccination Guidelines
The World Health Organization (WHO) recommends the RTS,S/AS01 malaria vaccine for children residing in regions with moderate to high Plasmodium falciparum malaria transmission. The schedule involves administering four doses, with the first dose given around 5 months of age. The initial three doses are given monthly, aiming for completion by 9 months of age.
A fourth dose is recommended between 15 and 18 months, or up to 22-24 months. This vaccine is intended to be integrated into routine childhood immunization programs to ensure broad and equitable coverage among the target population.
Impact on Malaria Control
Since its implementation, the RTS,S/AS01 vaccine has shown positive effects in areas where it has been rolled out. Pilot programs in Ghana, Kenya, and Malawi demonstrated the vaccine’s feasibility for delivery through routine immunization systems. These pilot evaluations also showed a reduction in severe malaria hospitalizations, with a reported 22% decrease.
The vaccine has contributed to a 13% drop in deaths from all causes among eligible children in these pilot areas. The vaccine has also increased equity in malaria prevention, reaching over two-thirds of children who do not consistently use insecticide-treated bed nets. Models suggest that widespread implementation of RTS,S/AS01 could avert between 200 and 700 deaths per 100,000 vaccinated children annually, potentially preventing 10-28% of all malaria deaths in children under five years of age.