The history of malaria vaccine development from 1960 to today's success.

Credit: Almeida, Maria & Vasconcelos, Maria & Tarragô, Andréa & Mariúba, Luís. (2021).
Circumsporozoite Surface Protein-based malaria vaccines: a review.
Revista do Instituto de Medicina Tropical de São Paulo. 63. 10.1590/s1678-9946202163011.

RTS,S/AS01 Vaccine

Over a dozen vaccine candidates are in clinical development, with two approved for children under five in high transmission areas. GlaxoSmithKline Biologicals' RTS,S/AS01 was the first to receive WHO recommendation in 2021. This vaccine has been in development since the mid-1980s, thanks to a public-private partnership involving GSKBio, PATH Malaria Vaccine Initiative, African research organizations, and funding from the Bill and Melinda Gates Foundation. After successful Phase 3 trials in seven countries, a large-scale pilot implementation provided conclusive evidence of its feasibility, safety, and impact, leading to WHO's recommendation.

A nurse gives the world's first malaria vaccine during a 2019 pilot program in Ghana.
The World Health Organization has since recommended this vaccine for use in
countries with moderate to high malaria transmission rates.
Cristina Aldehuela/AFP via Getty Images

Key Findings from RTS,S/AS01 Pilot

· Feasibility: The vaccine was effectively integrated into routine immunization systems, even during the COVID-19 pandemic.

· Equity: RTS,S increased access to malaria prevention, particularly for children not using ITNs.

· Safety: The vaccine has a favorable safety profile, with over 6 million doses administered by 2023 and no new safety issues.

· High Impact: The vaccine reduced clinical malaria by 39%, severe malaria by 30%, and all-cause mortality by 13%.

· Cost-effectiveness: The vaccine is cost-effective in moderate to high transmission areas.

Following WHO's recommendation, global health organizations, including GAVI, committed funding to support the vaccine's broader rollout. Due to immediate high demand, WHO and GAVI developed an equitable allocation framework and researched ways to extend the limited supply through fractionated doses.

Shipments of the world's first WHO-recommended malaria vaccine (RTS,S) to countries not part of the pilot vaccination programme,
have begun, with the first delivery made to Cameroon o­n the evening of November 21, 2023.
Credit: UNICEF/UNI474929/StoryMaxima

R21/Matrix-M Vaccine

WHO's recommendation of the R21/Matrix-M vaccine in 2023 is expected to increase vaccine availability for all children in malaria-endemic areas. Phase 2 and 3 trials showed it is safe, cost-effective, and highly efficacious, especially in highly seasonal malaria settings.

Global Health Implications

Malaria remains a significant burden, particularly in Africa, which accounted for 94% of cases and 95% of deaths in 2022. Despite efforts, malaria control progress has stalled, but the rollout of RTS,S/AS01 and the prequalification of R21/Matrix-M offer new hope.

Implementation Challenges

Limited production capacity and funding gaps pose challenges to widespread vaccine distribution. Countries need to prioritize who receives the vaccine and decide o­n booster doses. Combining vaccines with other interventions like ITNs and seasonal malaria chemoprevention can sustain protection.

Community Engagement

Effective malaria vaccine programs require community engagement, addressing vaccine hesitancy, and collaboration with cultural and religious leaders. Education campaigns and partnerships with communities are crucial for successful vaccine rollouts.

Future Directions

The Malaria Vaccine Technology Roadmap aims to develop highly effective vaccines by 2030, including those that reduce transmission and enable malaria elimination. Continued investment in vaccine development and support for global health organizations are essential for achieving these goals.