Tracking RTS,S, R21, and Next-Generation Malaria Vaccines
Malaria causes over 600,000 deaths annually, primarily among African children under 5. After decades of research, two vaccines have achieved WHO approval: RTS,S/AS01 (Mosquirix) in 2021 and R21/Matrix-M in 2023. RTS,S showed 30-40% efficacy in clinical trials and has been deployed in Ghana, Kenya, and Malawi since 2019. R21/Matrix-M demonstrated higher efficacy (up to 77%) in Phase 2b trials and is now scaling up production. This tracker monitors these approved vaccines plus emerging candidates including whole sporozoite vaccines (PfSPZ), viral vector vaccines, and novel mRNA platforms.
Developer: GlaxoSmithKline (GSK) / PATH Malaria Vaccine Initiative
Platform: Recombinant protein vaccine targeting P. falciparum circumsporozoite protein (CSP) with AS01 adjuvant
Efficacy: 30-40% against clinical malaria, 30% reduction in severe malaria in children aged 5-17 months (Phase 3 trials)
Dosing: 4-dose schedule (0, 1, 2 months, plus booster at 18-20 months)
Status: Deployed in Ghana, Kenya, Malawi since 2019. Over 2 million children vaccinated. WHO recommendation October 2021. Limited by moderate efficacy and complex dosing schedule.
Key Trials: Phase 3 trial across 7 African countries (15,000+ children), demonstrated safety and moderate efficacy. Real-world implementation ongoing through WHO pilot programs.
Developer: University of Oxford / Serum Institute of India (SII)
Platform: Virus-like particle (VLP) vaccine with Matrix-M adjuvant targeting CSP
Efficacy: 77% efficacy with seasonal booster in Phase 2b trials (Burkina Faso), 68-75% over 3 years with boosters
Dosing: 3-dose primary series (0, 1, 2 months) plus seasonal boosters
Status: WHO recommendation October 2023. Production scaling to 100-200 million doses annually at SII. Expected to significantly expand malaria vaccine access due to higher efficacy and manufacturing capacity.
Key Trials: Phase 3 trial in 4 African countries (4,800 children). Long-term follow-up studies ongoing. Age de-escalation studies in infants.
Developer: Sanaria Inc.
Platform: Whole sporozoite vaccine using radiation-attenuated live P. falciparum parasites
Efficacy: Up to 80% protection in controlled human malaria infection (CHMI) studies
Dosing: 5-dose direct venous inoculation (DVI) regimen
Status: Phase 3 trial in Equatorial Guinea and Tanzania (3,600 participants). Addresses administration challenges for field deployment. Previous CHMI studies showed high protective efficacy.
Challenge: Requires direct venous inoculation and cryopreservation, limiting field deployment feasibility.
Developer: University of Oxford
Platform: Prime-boost viral vector vaccine using chimpanzee adenovirus (ChAd63) and modified vaccinia Ankara (MVA)
Target: Multiple P. falciparum antigens including ME-TRAP
Status: Phase 2b efficacy trial in Kenya (450 participants). Aims to induce T-cell immunity complementing antibody-based vaccines.
Developer: African Malaria Network Trust (AMANET)
Platform: Blood-stage vaccine targeting GLURP and MSP3 proteins
Goal: Prevent disease rather than infection by targeting blood-stage parasites
Status: Phase 2b trial in Burkina Faso and Gabon (1,200 participants) testing in combination with seasonal malaria chemoprevention (SMC).
Developer: BioNTech
Platform: mRNA technology encoding P. falciparum circumsporozoite protein (CSP)
Status: Phase 1 trial in Germany and Gabon (120 participants). First mRNA malaria vaccine to enter clinical testing. Evaluating multiple dose levels and schedules.
Innovation: Applies proven mRNA platform from COVID-19 vaccines to malaria. Potential for rapid development and manufacturing scale-up.
Developer: Sanaria Inc.
Platform: Chemoprophylaxis vaccination using live sporozoites with antimalarial drug coverage
Status: Phase 2 trial in Tanzania (300 participants) optimizing regimens for field deployment.
Concept: Uses live parasites under drug coverage to generate immunity, showing high efficacy in controlled settings.
Developer: Seattle Children's Research Institute
Platform: Genetically attenuated parasite (GAP) with three gene deletions
Status: Phase 1 trial in USA and Tanzania (80 participants). Testing safety and protective efficacy in CHMI studies.
Innovation: Uses genetic modification instead of radiation for attenuation.
Malaria vaccine development faces unique challenges: the parasite's complex life cycle, extensive antigenic variation, and incomplete understanding of protective immunity. Current vaccines provide moderate protection requiring multiple doses and boosters. The 2023 WHO approval of R21/Matrix-M represents significant progress, but achieving high-efficacy, durable protection remains the ultimate goal. Combination approaches and next-generation platforms offer hope for breakthrough vaccines.