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

Infant Malaria Vaccine Schedule Optimization (clinicaltrials.gov) - P2 | N=1200 | Recruiting | Sponsor: PATH | Trial completion date: Nov 2027 ➔ Mar 2028 | Trial primary completion date: Nov 2027 ➔ Mar 2028

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

Performance characteristics and potential public health impact of improved pre-erythrocytic malaria vaccines targeting childhood burden. (PubMed, PLOS Glob Public Health) - "New malaria vaccine development builds on groundbreaking recommendations and roll-out of two approved pre-erythrocytic vaccines (PEVs); RTS,S/AS01 and R21/Matrix-M...The contribution of each property to the overall impact varies by setting and clinical endpoint, indicating that public health goals should dictate key vaccine performance criteria. Overall, our findings support the need for well-defined target product profiles for long duration vaccines linking priority use cases of where, how, and to whom to deploy new malaria vaccines, to maximize public health impact."

Journal • Infectious Disease • Malaria • FPR2

Mitigation of Malaria in Sub-Saharan Africa through Vaccination: A Budding Road Map for Global Malaria Eradication. (PubMed, Ethiop J Health Sci) - "Other candidates such as R21/Matrix-M showed up to 77% efficacy in trials...Strengthening healthcare infrastructure, amplifying vaccine acceptance campaigns, and increasing funding for research and vaccine production are pivotal. Malaria vaccination offers a practical and sustainable pathway toward global malaria elimination and the realization of SDG 3 by 2030."

Journal • Review • Infectious Disease • Malaria

Subnational introduction of the RTS,S/AS01E malaria vaccine into routine immunization: experience and lessons from the three pilot countries. (PubMed, Malar J) - "The pilot highlighted lessons for malaria vaccine introduction: (1) clearly outlined roles and responsibilities of key stakeholders including NIP and National Malaria Programme (NMP); (2) appropriate approach to vaccine introduction launch, communication, and demand generation to enhance vaccine uptake; (3) flexibility with dose scheduling to optimize coverage; and (4) updated data collection tools for accurate documentation, and data quality."

Journal • Infectious Disease • Malaria

Repertoire, function, and structure of serological antibodies induced by the R21/Matrix-M malaria vaccine. (PubMed, J Exp Med) - "NANP-specific IGHV3-30/3-33 mAbs mined from polyclonal IgG repertoires blocked sporozoite invasion in vitro and prevented parasitemia in vivo. Overall, R21/Matrix-M elicits polarized, minimally mutated, polyclonal IgG responses that can target multiple protective CSP epitopes, offering molecular insight into the serological basis for its demonstrated efficacy against P. falciparum malaria."

Journal • Infectious Disease • Malaria

Dose Finding Trial of R21/Matrix-M in School Children (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: University of Oxford

New P2 trial • Infectious Disease • Malaria

R21/Matrix-M malaria vaccine drives diverse immune responses in pre-exposed adults: insights from a phase IIb controlled human malaria infection trial. (PubMed, Front Immunol) - "We provide insights into the diverse immune responses induced by R21/Matrix-M vaccination and their potential contribution to protection against malaria. These findings highlight the potential of the R21/Matrix-M vaccination and protection in adults with varying levels of prior malaria exposure."

Journal • P2b data • Infectious Disease • Malaria • CXCR5 • PD-1

R21/Matrix-M in African Children Against Clinical Malaria (clinicaltrials.gov) - P3 | N=4800 | Active, not recruiting | Sponsor: University of Oxford | Trial completion date: Mar 2026 ➔ Sep 2027

Trial completion date • Infectious Disease • Malaria

Vaccine-induced responses to R21/Matrix-M - an analysis of samples from a phase 1b age de-escalation, dose-escalation trial. (PubMed, Front Immunol) - "This could thus inform the development of next-generation malaria vaccines. However, additional crucial factors need further exploration."

Journal • P1 data • Infectious Disease • Malaria

COSAV-R21: Comparison of Two Strategies for Administering the R21-Matrix M Vaccine in a Context of Seasonal Malaria Transmission in Chad (clinicaltrials.gov) - P4 | N=70000 | Not yet recruiting | Sponsor: Epicentre

New P4 trial • Infectious Disease • Malaria

Malaria Vaccines and Global Equity: A Scoping Review of Current Progress and Future Directions. (PubMed, Biomedicines) - "This progress continued with the 2023 approval of the R21/Matrix-M vaccine, which is more cost-effective, more potent due it is higher protein content, and easier to manufacture...Search and Boolean search terms were modified to include terms like "malaria vaccines", "malaria vaccination", "malaria immunisation", "malaria immunisation AND malaria-endemic countries", "malaria endemic low-income countries AND malaria control", "malaria public health control", "malaria chemoprophylaxis AND early diagnosis of malaria", "screening for malaria", and "laboratory diagnosis of malaria in endemic countries" in order to find pertinent studies. Preliminary insights suggest that although vaccines are crucial, comprehensive strategies involving health education, hygiene, and timely medical intervention remain essential to malaria control."

Journal • Review • Infectious Disease • Malaria

Malaria vaccine implementation in Nigeria: Addressing the coverage challenges within the national immunization program for high impact. (PubMed, Vaccine) - "The malaria vaccines, RTS,S/AS01 and R21/Matrix-M, bring fresh hope to curbing malaria mortality globally, especially among children below age five who are most susceptible...It draws from review-level evidence to propose four priority areas for improvement within the NPI to achieve a high-impact implementation-i.e., Reach Maximization, Social Mobilization, Program Management, and Progress Monitoring-in line with global immunization strategy frameworks. Evidence-based strategies to influence these domains in the Nigerian context are emphasized."

Journal • Infectious Disease • Malaria

An Observational Study to Assess Effectiveness and Safety of The R21/Matrix-M Malaria Vaccine (clinicaltrials.gov) - P=N/A | N=2308 | Not yet recruiting | Sponsor: Serum Institute of India Pvt. Ltd.

New trial • Infectious Disease • Malaria

Infant Malaria Vaccine Schedule Optimization (clinicaltrials.gov) - P2 | N=1200 | Recruiting | Sponsor: PATH | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Malaria

Exploring the role of Plasmodium circumsporozoite-specific ZEB2+ cytolytic effector memory CD4+ T cells in protection against malaria (IMMUNOLOGY 2025) - "The two WHO-approved vaccines (RTS,S/AS01 and R21/Matrix-M) both target the circumsporozoite protein (CSP) antigen of the Plasmodium falciparum parasite...Using radiation-attenuated sporozoite immunization in ZEB2 reporter and loss-of-function mouse models, we are investigating if ZEB2+ CD4+ T cells differentiate, establish liver residency, and protect against live infection. Taken together, we will be discussing whether ZEB2+ CD4+ T cells may represent new correlates of protection in malaria.Keywords: Animals Human Rodent; Cells T Cells, Cytotoxic; Molecules T Cell Receptors; Processes Memory"

Infectious Disease • Malaria • CD4 • ZEB2

VAC093: A Study to Assess the Experimental Malaria Vaccines R78C and RH5.1 Combined With R21/Matrix-M (a "Multi-stage" Malaria Vaccine) (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: University of Oxford

New P1 trial • Infectious Disease • Malaria

Nurses' knowledge and willingness to recommend malaria vaccination to caregivers of under-5 in Nigeria: a nationwide survey. (PubMed, Malar J) - "The findings highlight major gaps in Nigerian nursing's knowledge and awareness of malaria vaccinations, as well as their willingness to recommend the vaccine to parents. Addressing these gaps will enable nurses to play a critical role in the successful implementation of malaria immunization campaigns, lowering the illness burden among vulnerable populations."

Journal • Infectious Disease • Malaria

Dose-Escalating Study of Pfs230D1 in Combination With R21 in Matrix-M in African Adults (clinicaltrials.gov) - P1 | N=240 | Active, not recruiting | Sponsor: Serum Institute of India Pvt. Ltd. | Trial primary completion date: Apr 2025 ➔ Oct 2025 | Not yet recruiting ➔ Active, not recruiting

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

First Malaria Vaccine RTS, S: A Step toward the Eradication of Malaria. (PubMed, Arch Razi Inst) - "RTS,S is a significant initial step in the path to the production of other highly protective and multi-stage vaccines that may become part of malaria eradication programs in the near future. Several malariologists are working on the early clinical development or trial phases of first-generation and next-generation malaria vaccines, such as R21/Matrix-M, using mRNA technology."

Journal • Infectious Disease • Malaria • Novel Coronavirus Disease

Current Developments in Malaria Vaccination: A Concise Review on Implementation, Challenges, and Future Directions. (PubMed, Clin Pharmacol) - "The introduction of pre-erythrocytic malaria vaccines (RTS,S/AS01 and R21/Matrix-M), represents an important milestone in malaria control efforts with promising results from the erythrocytic vaccine RH5.1/Matrix-M in recent clinical trials...There is a critical need to integrate malaria vaccination efforts with established malaria control interventions (eg, insecticide-treated bed nets, vector control strategies, and anti-malarial drugs). Achieving sustained control of malaria morbidity and mortality will require strong global collaboration, sufficient funding, and continuous efforts to address inequities in access and delivery of malaria control measures including the malaria vaccines."

Journal • Review • Infectious Disease • Malaria

A Study to Assess the Experimental Malaria Vaccines RH5.2-VLP and R21 (clinicaltrials.gov) - P1 | N=107 | Active, not recruiting | Sponsor: University of Oxford | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Malaria

Infant Malaria Vaccine Schedule Optimization (clinicaltrials.gov) - P2 | N=1200 | Not yet recruiting | Sponsor: PATH

New P2 trial • Infectious Disease • Malaria

Novel, fully human, anti-PfCSP antibodies with potent antimalarial activity using a phage display based strategy. (PubMed, Vaccine) - "The circumsporozoite protein (CSP) is a major surface protein of the sporozoites, and is the target of two licensed Plasmodium falciparum malaria vaccines, RTS,S/AS01, named Mosquirix and R21/Matrix-M. Low-dose passive transfer of the CL1 and CL3 antibodies conferred high-level protection when challenged with PfCSP-Pb transgenic parasites in the mouse infection model. The high in vitro and in vivo efficacies of the CL1 and CL3 antibodies have applications in malaria immunoprophylaxis in protecting travellers and military servicemen or as a therapeutic vaccine in malaria elimination programmes."

Journal • Infectious Disease • Malaria

IMVACS: Integrating Malaria Vaccine with Seasonal Malaria Chemoprevention in West Africa (clinicaltrials.gov) - P4 | N=40000 | Not yet recruiting | Sponsor: Epicentre

New P4 trial • Infectious Disease • Malaria

MVDA: Mass Vaccine and Drug Administration, Bangladesh (clinicaltrials.gov) - P4 | N=10000 | Recruiting | Sponsor: University of Oxford | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Malaria