RTS,S Malaria Vaccine

The RTS,S malaria vaccine, marketed under the trade name Mosquirix, is the first vaccine developed to provide partial protection against malaria in humans. It targets Plasmodium falciparum, the deadliest malaria parasite and the most prevalent in sub-Saharan Africa. Developed through a partnership between GlaxoSmithKline (GSK), the PATH Malaria Vaccine Initiative, and other research institutions, it represents a landmark in global health as the first approved vaccine for a parasitic disease.

Background

Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites transmitted through the bites of female Anopheles mosquitoes. Globally, malaria remains a major public health challenge, causing significant morbidity and mortality, particularly among young children and pregnant women in Africa.
For decades, malaria control relied heavily on preventive measures such as insecticide-treated bed nets, indoor residual spraying, and antimalarial drugs. However, the development of vaccine-based protection has been a key scientific objective due to the persistent burden of the disease and emerging resistance to insecticides and antimalarial drugs.

Vaccine Design and Mechanism

The RTS,S vaccine is based on recombinant protein technology and specifically targets the circumsporozoite protein (CSP), a surface protein of Plasmodium falciparum sporozoites.

• RTS Component: This segment is a fusion of part of the CSP with the hepatitis B surface antigen (HBsAg), providing both antigenic stimulation and structural stability.
• S Component: An additional HBsAg element that helps form virus-like particles, enhancing the immune response.
• Adjuvant AS01: A proprietary adjuvant system containing MPL (a detoxified form of lipopolysaccharide) and QS-21 (a saponin extract), designed to boost immunogenicity.

Upon vaccination, the immune system generates antibodies and T-cell responses against CSP, aiming to block the parasite at the sporozoite stage before it infects liver cells.

Clinical Development

The vaccine’s development spanned over 30 years, involving extensive preclinical and clinical studies.

• Phase III Trials: Conducted between 2009 and 2014 across several African countries, enrolling over 15,000 infants and young children.
• Efficacy: Trials demonstrated approximately 39% reduction in malaria cases and 29% reduction in severe malaria in children aged 5–17 months after four doses. Efficacy was lower in infants aged 6–12 weeks.
• Durability: Protection wanes over time, with booster doses required to maintain efficacy.

WHO Approval and Implementation

• In 2015, the European Medicines Agency (EMA) issued a positive scientific opinion on RTS,S.
• In 2019, pilot vaccination programmes began in Ghana, Kenya, and Malawi under WHO coordination.
• In October 2021, the World Health Organization recommended the broad use of RTS,S for children in sub-Saharan Africa and other regions with high P. falciparum transmission.

This marked the first time a malaria vaccine received a global health recommendation.

Administration Schedule

The full course of RTS,S requires four doses:

1. Three initial doses given one month apart, starting at 5–17 months of age.
2. A fourth booster dose administered around 18 months after the third.

This schedule aligns with routine childhood immunisation programmes.

Public Health Impact

The RTS,S vaccine provides only partial protection, yet its impact is considered significant when integrated with other malaria control strategies.

• Projected Benefits: Modelling studies suggest that widespread use could prevent millions of cases and thousands of child deaths annually.
• Target Population: Particularly beneficial for children under five, who represent the majority of malaria deaths.
• Complementary Role: It is not a replacement for existing preventive methods but adds another layer of protection in malaria control strategies.

Limitations

While RTS,S marks a breakthrough, it has limitations:

• Partial Efficacy: Provides less protection than most viral or bacterial vaccines.
• Waning Immunity: Requires booster doses for sustained effect.
• Logistical Challenges: Distribution, cost, and integration into existing immunisation schedules present hurdles.
• Strain-Specific Protection: Primarily effective against P. falciparum, with limited utility in regions dominated by other Plasmodium species.

Future Developments

RTS,S is a foundation for future malaria vaccine research. Other candidates are under investigation, including:

• R21/Matrix-M Vaccine: A newer malaria vaccine candidate showing higher efficacy in recent trials.
• mRNA-based Platforms: Experimental vaccines leveraging mRNA technology to target malaria parasites.
• Combination Strategies: Approaches combining vaccination with chemoprevention and genetic mosquito control.