RTS,S

RTS,S, also known by its trade name Mosquirix, is the world’s first vaccine developed to provide protection against malaria, a life-threatening disease caused by the parasite Plasmodium falciparum. It represents a major breakthrough in global public health and infectious disease control, particularly in sub-Saharan Africa, where malaria continues to be a leading cause of illness and death among young children.
The vaccine was developed through a collaboration between GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative (MVI), with significant support from the Bill & Melinda Gates Foundation and coordination from the World Health Organization (WHO). RTS,S marks the culmination of over three decades of research, becoming the first malaria vaccine to be recommended by the WHO for widespread use.

Development and Background

The development of RTS,S began in the 1980s, with researchers seeking a vaccine capable of targeting the early stages of Plasmodium falciparum infection—the most deadly malaria parasite species affecting humans. After decades of clinical research, the vaccine entered large-scale trials in Africa, involving over 15,000 infants and young children across seven countries.
The trials demonstrated that RTS,S could significantly reduce episodes of malaria, severe malaria, and malaria-related hospital admissions when administered in multiple doses. Based on these findings, the European Medicines Agency (EMA) issued a positive scientific opinion on RTS,S in 2015, and the WHO recommended its pilot introduction in 2019.
The vaccine became the first ever approved for use against a parasitic disease in humans—a milestone in global immunisation efforts.

Composition and Mechanism of Action

RTS,S is a recombinant protein-based vaccine, meaning it is produced through genetic engineering rather than using live or weakened parasites.

• RTS represents parts of the Plasmodium falciparum circumsporozoite protein (CSP), found on the surface of the malaria parasite during its sporozoite stage (when it enters the human liver).
• S denotes the hepatitis B surface antigen, which serves as a carrier and enhances the immune response.
• The vaccine is combined with AS01, a proprietary adjuvant developed by GSK that strengthens the immune response.

The vaccine works by stimulating the body’s immune system to produce antibodies and T-cell responses that attack the malaria parasite before it can infect liver cells and multiply. This mechanism interrupts the parasite’s life cycle, preventing the disease from progressing to the symptomatic stage.

Administration and Dosage

RTS,S is recommended for use in children living in malaria-endemic regions, where the risk of infection is highest. The WHO advises the following schedule:

• Four doses in total: three doses administered one month apart, beginning at about 5 months of age, followed by a fourth booster dose at around 18 months.

The four-dose schedule is crucial to achieving optimal and sustained protection.

Effectiveness and Impact

Clinical trials and pilot programmes have shown that RTS,S:

• Reduces clinical malaria cases by about 40% after four doses.
• Decreases severe malaria cases by around 30%.
• Reduces malaria-related hospitalisations and deaths significantly when combined with other control measures.

Although the protection level is modest compared to vaccines for other diseases, its public health impact is substantial given the high malaria burden in affected regions. When integrated with existing interventions such as insecticide-treated bed nets and anti-malarial drugs, RTS,S offers a powerful additional tool to combat the disease.
Pilot implementation in Ghana, Kenya, and Malawi under the Malaria Vaccine Implementation Programme (MVIP) confirmed the vaccine’s feasibility, safety, and effectiveness in real-world conditions. Following these results, the WHO officially recommended in October 2021 the widespread use of RTS,S for children in areas with moderate to high malaria transmission.

Global Implementation and Distribution

Following WHO’s endorsement, RTS,S began wider rollout across several African countries, supported by Gavi, the Vaccine Alliance, UNICEF, and national health ministries.
Key milestones include:

• 2022–2023: Introduction in countries such as Ghana, Kenya, and Malawi, with hundreds of thousands of children vaccinated.
• 2024 onward: Expanded access across sub-Saharan Africa, targeting millions of children annually.
• Production and Supply: GSK manufactures RTS,S, while efforts are underway to transfer technology and expand production capacity through partners such as Bharat Biotech in India.

This scale-up aims to integrate RTS,S into routine immunisation programmes in malaria-endemic regions.

Limitations and Challenges

While RTS,S marks a major advance, several challenges remain:

• Partial Efficacy: The vaccine does not provide complete protection, and immunity wanes over time, necessitating booster doses.
• Logistical Complexity: The four-dose regimen requires strong healthcare delivery systems and sustained community engagement.
• Cost and Supply Constraints: Manufacturing capacity and funding are still limited compared to global demand.
• Complementary Measures Needed: RTS,S must be used alongside existing control tools such as bed nets, vector control, and prompt diagnosis and treatment.

Despite these challenges, modelling studies suggest that widespread use of RTS,S could prevent tens of thousands of deaths each year among children under five in high-transmission areas.

Future Developments

The success of RTS,S has paved the way for next-generation malaria vaccines. The most notable among these is R21/Matrix-M, developed by the University of Oxford and the Serum Institute of India, which has demonstrated higher efficacy in clinical trials. However, RTS,S remains a foundational achievement and continues to play a key role in the global fight against malaria.
Research continues on improving vaccine formulations, durability of protection, and integration with other malaria control strategies.

Significance in Global Health

RTS,S represents a historic scientific and humanitarian milestone. It is the first vaccine to target a parasitic disease, demonstrating the potential of biotechnology in addressing complex infectious diseases that disproportionately affect low-income regions.
Its introduction signifies progress toward the goals of the WHO Global Technical Strategy for Malaria 2016–2030, which seeks to reduce malaria incidence and mortality by at least 90%.