R21/Matrix-M / University of Oxford, Serum Institute of India - LARVOL DELTA

Nanoparticle based drug delivery systems improve antimalarial efficacy and vaccine performance in African research and clinical settings. (PubMed, Discov Nano) - "Nanoparticle drug delivery demonstrates potentials in improving antimalarial efficacy, targeting, and safety, yet translation remains limited by manufacturing scale-up, regulatory gaps, and a lack of long-term toxicity data. Strengthening local production and South-South/North-South collaborations is essential to integrating these technologies into Africa's malaria control programmes."

Journal • Review • Immune Modulation • Immunology • Infectious Disease • Malaria

Status of Malaria Vaccine Introduction-Africa, 2019-2024. (PubMed, Am J Trop Med Hyg) - "There are two malaria vaccines prequalified by the WHO: RTS,S/AS01 and R21/Matrix-M...During 2023-2024, a total of 13,250,098 vaccine doses were shipped to countries. The introduction of the malaria vaccine presents an integration opportunity with preventive health services to reduce child morbidity and mortality."

Journal • Infectious Disease • Malaria

Progress in Malaria Prevention. (PubMed, Annu Rev Med) - "The licensure of two preerythrocytic vaccines, RTS,S/AS01 and R21/Matrix-M, represents a major milestone, providing partial but meaningful protection against clinical malaria, especially when integrated with other control strategies...These developments underscore the importance of layered, context-specific malaria prevention strategies that integrate vaccines, chemoprevention, and vector control. Sustained innovation, funding, and implementation will be essential to accelerate progress toward malaria control and elimination."

Journal • Review • Infectious Disease • Malaria

Clinical efficacy, immunogenicity and safety of RTS,S/AS01, R21/Matrix-M and candidate malaria vaccines in children: A systematic review and meta-analysis. (PubMed, J Infect Public Health) - "Malaria vaccines in children show a favorable safety profile and provide meaningful although time-limited protection against clinical malaria. RTS,S and R21 vaccines achieve the highest efficacy particularly in combination with SMC. Malaria vaccination should be integrated into childhood malaria control strategies emphasizing the need for booster strategies and long-term effectiveness monitoring in endemic settings."

Journal • Retrospective data • Infectious Disease • Malaria • Pediatrics

Malaria Vaccine Rollout in Nigeria: Current Status and Challenges. (PubMed, Am J Trop Med Hyg) - "The introduction of RTS,S/AS01, and R21/Matrix-M vaccines provides a promising complementary prevention strategy...Advocacy and social mobilization were at 0% across all three facilities, and monitoring and supervision ranged from 0% to 33%, all far below the WHO-recommended 95% threshold. Strengthening health systems, targeted communication, and sustainable public financing are essential for a successful nationwide malaria vaccine rollout."

Journal • Infectious Disease • Malaria

Update on malaria vaccines deployment and challenges in the field. (PubMed, Clin Microbiol Infect) - "The roll-out of the first two malaria vaccines at large scale is progressing rapidly in sub-Saharan Africa, with 25 countries having introduced the vaccines in their routine immunization programs as of February 2026. However, current implementation challenges including funding constraints, manufacturing capacity, delivery strategies and vaccine hesitancy should be quickly addressed to gain significant impact in targeted populations. Next-generation vaccines might improve the protective efficacy and durability against clinical malaria and reduce the transmission activity of the vectors to support global elimination efforts."

Journal • Review • Infectious Disease • Malaria

Dose Finding Trial of R21/Matrix-M in School Children (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: University of Oxford | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2026 ➔ Mar 2027

Enrollment closed • Trial primary completion date • Infectious Disease • Malaria

Quantitative and Clinical Pharmacology Perspectives on Next-Generation Malaria Prevention Using Vaccines and Long-Acting Monoclonal Antibodies. (PubMed, Clin Transl Sci) - "Vaccines such as RTS,S/AS01 and R21/Matrix-M induce active immunity through polyclonal antibody and CD4+ T-cell responses against the circumsporozoite protein (CSP), providing durable, population-level protection. In contrast, mAbs including CIS43LS and L9LS confer immediate, passive immunity, with protection directly linked to systemic exposure and duration above protective thresholds...This review emphasizes how quantitative PK/PD and PBPK modeling provide a framework to optimize dosing, predict durability of protection, and guide clinical development across diverse populations. These strategies underscore the value of model-informed translational pharmacology in accelerating development of next-generation malaria preventive interventions against malaria."

Journal • Review • Infectious Disease • Malaria • Pediatrics • CD4

Assessing Vaccine Effectiveness of R21/Matrix-M Across Malaria Transmission Settings (AVERT) (clinicaltrials.gov) - P=N/A | N=20000 | Recruiting | Sponsor: Clinton Health Access Initiative Inc.

New trial • Real-world evidence • Infectious Disease • Malaria

VAC100: R21/MM Dosing, Presentations, and Preservatives (clinicaltrials.gov) - P4 | N=375 | Not yet recruiting | Sponsor: University of Oxford | Initiation date: Apr 2026 ➔ Aug 2026

Head-to-Head • Trial initiation date • Infectious Disease • Malaria

Who will pay for the malaria vaccines in Africa? (PubMed, Arch Public Health) - "The World Health Organization's endorsement of the RTS, S/AS01 vaccine in October 2021 and the R21/Matrix-M vaccine in October 2023 represents a major scientific advance; however, the central question confronting African policymakers, donors, and governments is no longer scientific but financial...Coordinated action by donors, governments, and manufacturers, including predictable multi-year financing, differential pricing, and measurable domestic allocations, is needed to prevent distribution by purchasing power rather than by epidemiological need. This comment aims to examine who will finance malaria vaccines in Africa and how equitable and sustainable delivery can be secured."

Journal • Infectious Disease • Malaria • Novel Coronavirus Disease

Awareness and acceptance of malaria vaccines by caregivers of under-5 children in Abia State, Nigeria: a mixed methods study. (PubMed, BMJ Public Health) - "The 2024 introduction of the R21/Matrix-M and RTS,S/AS01 vaccines offers promise, but evidence on caregiver awareness and acceptance in the non-pilot South-East region to inform equitable rollout is scarce...Based on our findings, caregivers demonstrated strong acceptance of malaria vaccines despite critically low awareness, a disparity fuelled by information gaps and socio-demographic inequities such as low education and rural residence that threaten vaccine rollout and malaria elimination goals. Consequently, this pioneering mixed-methods study recommends that specific channels that leverage primary healthcare centre providers and community leaders for information dissemination should be used, given the high levels of trust, to ensure malaria vaccine uptake and accelerate progress in reducing under-5 deaths."

Journal • Infectious Disease • Malaria

Epitope-selective vaccine designs to elicit protective antibodies against the Plasmodium falciparum circumsporozoite protein. (PubMed, NPJ Vaccines) - "Recently introduced malaria vaccines, RTS,S/AS01 and R21/Matrix-M, are effective in preventing infection, but their efficacy declines over time...No construct was found to be superior to the clinical benchmark RTS,S/AS01 in the mouse model. These results can inform approaches to malaria vaccine design and direct future research."

Journal • Infectious Disease • Malaria

Structure and functional diversity of antibodies targeting the P. falciparum circumsporozoite protein C-terminal domain. (PubMed, bioRxiv) - "WHO-recommended vaccines RTS,S/AS01 E and R21/Matrix-M target the Pf CSP major repeat region and C-terminal domain (ctCSP)...In vitro, ctCSP mAbs promoted stronger Fc-receptor signaling, cellular cytotoxicity, and phagocytosis than repeat region mAbs, while mAb combinations targeting distinct Pf CSP epitopes modulated Fc-signaling and cellular cytotoxicity. This study provides a rationale for optimization of Pf CSP-based immunogens to enhance Fc-mediated contributions to malaria vaccine efficacy."

Journal • Infectious Disease • Malaria

The Malaria Vaccine Implementation Programme reduced clinical malaria in Kenya, 2020 to 2022 : Impact evaluation with predictive time-series models of routine surveillance data. (PubMed, Malar J) - "This analysis revealed that routine health data, although age-aggregated to both vaccine eligible and noneligible children < 5 years, demonstrated a reduction in malaria cases throughout the evaluation period. A further reduction in cases was observed as more vaccine-eligible children comprised the under 5 population. High quality routine data can be used to monitor vaccine impact on clinical malaria."

Journal • Infectious Disease • Malaria

Advances in the development of malaria vaccines. (PubMed, BMJ) - "In Africa, where the burden of malaria is the highest, the implementation of the RTS,S/AS01 and R21/Matrix-M vaccines through national Expanded Program on Immunization schedules is under way, underscoring the importance of community engagement and health system readiness while highlighting the need for next generation vaccines with greater durability and breadth. Achieving elimination of malaria requires improving current vaccine strategies, integrating novel technologies, and strengthening delivery mechanisms in endemic regions to overcome both biological and operational barriers."

Journal • Review • Infectious Disease • Malaria

Bivalent virus-like particles expressing SPECT1 and CSP trigger pre-erythrocytic malaria immunity and protect against transgenic Plasmodium falciparum sporozoite challenge in mice. (PubMed, Front Immunol) - "The decline in protective antibody titers and efficacy over time of the circumsporozoite protein (CSP)-based RTS,S/AS01 and R21/Matrix-M vaccines highlights the need for improved vaccines...Our findings show that PfSPECT-1 can be effectively incorporated into the HBsAg VLPs and co-displayed with CSP epitopes without impairing immunogenicity. Although protection was evaluated using transgenic P. berghei parasites expressing P. falciparum antigens, the modular HBsAg VLP platform theoretically allows incorporation of antigens from other Plasmodium species such as P. vivax."

Journal • Preclinical • Hepatitis B • Infectious Disease • Inflammation • Malaria

Infant Malaria Vaccine Schedule Optimization (clinicaltrials.gov) - P2 | N=964 | Recruiting | Sponsor: PATH | Trial completion date: Mar 2028 ➔ Sep 2027 | Trial primary completion date: Mar 2028 ➔ Sep 2027

Trial completion date • Trial primary completion date • Infectious Disease • Malaria

A Study to Assess the Experimental Malaria Vaccines RH5.2-VLP and R21 (clinicaltrials.gov) - P1 | N=107 | Completed | Sponsor: University of Oxford | Active, not recruiting ➔ Completed | Trial completion date: Dec 2027 ➔ Dec 2025 | Trial primary completion date: Dec 2027 ➔ Dec 2025

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Malaria

Malaria Prevention: Progress to Date. (PubMed, Drugs) - "The World Health Organization-endorsed RTS,S/AS01 (Mosquirix®) and R21/Matrix-M vaccines rolled out in many highly malaria-endemic sub-Saharan African countries, in addition to other malaria control tools, provide overall moderate protection in young children but significantly reduce severe disease and death, and are considered safe. The evolution of malaria preventive tools is a dynamic process, with numerous novel developments on the horizon. For travel medicine indications, further harmonisation of recommendations on the one hand, but also more sophisticated personalisation of recommendations, is envisaged."

Journal • Infectious Disease • Malaria

Protective immunity against malaria by a nanoparticle CIS43-based junctional vaccine alone or in combination with R21. (PubMed, NPJ Vaccines) - "Repetitive display of the major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) is the basis for two WHO-recommended vaccines: RTS,S/AS01 and R21/Matrix-M...In vivo B cell analysis and isolation of monoclonal antibodies confirmed differences in vaccine-induced antibody specificities. Altogether, these data suggest the nanoparticle-formatted tandem-repeated CIS43-junctional vaccine to be a promising approach to broaden immunity against malaria, either as a standalone intervention or in combination with R21."

Journal • Infectious Disease • Malaria

Awareness, acceptability and determinants of the new malaria vaccine among caregivers of under-five children in Asaba, Nigeria: a multi-centre cross-sectional study. (PubMed, Malar J) - "Despite a strong willingness among caregivers to vaccinate their children, awareness of the malaria vaccine was inadequate. Targeted awareness campaigns, especially addressing safety concerns and spousal engagement, are urgently needed to translate high willingness into actual uptake."

Journal • Observational data • Infectious Disease • Malaria

Efficacy and immunogenicity of RTS,S/AS01 and R21/Matrix-M malaria vaccines: - Systematic review and meta-analysis. (PubMed, J Infect Public Health) - "As compared to prior reviews, our study highlights that both of the two breakthrough vaccines are paving the way for total malaria elimination and reduction in morbidity and mortality."

Journal • Retrospective data • Infectious Disease • Malaria

Designing a next-generation multi-stage vaccine for malaria prevention. (PubMed, Microb Pathog) - "To date, only two vaccines, RTS,S/AS01 and R21/Matrix-M, are recommended by the WHO...In silico cloning indicated its potential for efficient expression in E. coli. The proposed vaccine construct has shown promising results; however, in vitro and in vivo studies are necessary to validate its efficacy."

Journal • Infectious Disease • Malaria • TLR4

L9LS-R21 Interaction (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=357 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Infectious Disease • Malaria