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

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

A Study to Determine if New Types of Malaria Vaccines Are Safe, Effective and Lead to Immunity in Kenyan Adults (clinicaltrials.gov) - P2 | N=80 | Terminated | Sponsor: University of Oxford | Phase classification: P2b ➔ P2 | Recruiting ➔ Terminated; Due to US FDA hold on the challenge agent and funding concerns

Phase classification • Trial termination • Infectious Disease • Malaria

Unlocking the potential of blood-stage vaccines for malaria elimination. (PubMed, Trans R Soc Trop Med Hyg) - "Currently, pre-erythrocytic vaccines like RTS, S/AS01 and R21/Matrix-M are in use, but their effectiveness is limited...Understanding the structural biology and immunological interactions of blood-stage antigens is essential for developing effective vaccines. Combining pre-erythrocytic and erythrocytic-stage vaccines could lead to better protection, improved public health outcomes and significant progress toward malaria elimination."

Journal • Infectious Disease • Malaria

Acceptability of the R21/Matrix-M malaria vaccine alongside existing malaria interventions in the trial context. (PubMed, BMJ Glob Health) - "The R21/Matrix-M vaccine was acceptable to caregivers and communities of participants in the R21/Matrix-M phase III trial in Mali. Implementation research is needed to evaluate and ensure co-coverage of complementary malaria control interventions, including SMC in seasonal settings, in the face of the scale-up of R21/Matrix-M and other malaria vaccines."

Clinical • Journal • Infectious Disease • Malaria

The R21/Matrix-M malaria vaccine: questions remain. (PubMed, Lancet) - No abstract available

Journal • Infectious Disease • Malaria

The R21/Matrix-M malaria vaccine: questions remain. (PubMed, Lancet) - No abstract available

Journal • Infectious Disease • Malaria

The R21/Matrix-M malaria vaccine: questions remain - Author's reply. (PubMed, Lancet) - No abstract available

Journal • Infectious Disease • Malaria

The R21/Matrix-M malaria vaccine: questions remain. (PubMed, Lancet) - No abstract available

Journal • Infectious Disease • Malaria

Integrating malaria vaccine and CRISPR/Cas9 gene drive: a comprehensive strategy for accelerated malaria eradication. (PubMed, Malar J) - "Recent advancements, including the rollout of malaria vaccines, such as RTS,S/AS01 and R21/Matrix-M™, offer new avenues for prevention...Challenges such as regulatory hurdles, community acceptance, ecological impacts, and sustainable funding are examined, alongside strategies for implementation within existing malaria control programmes. This integrated approach could significantly contribute to achieving the World Health Organization's targets for malaria reduction by 2030, ultimately enhancing public health outcomes and supporting broader socio-economic development."

Journal • Review • Infectious Disease • Malaria

Roll out and prospects of the malaria vaccine R21/Matrix-M. (PubMed, PLoS Med) - "In this Perspective article, Lorenz von Seidlein outlines the promise of two malaria vaccines, and discusses some of the considerations for their roll out."

Journal • Infectious Disease • Malaria

Evaluation of a novel malaria anti-sporozoite vaccine candidate, R21 in Matrix-M adjuvant, in the UK and Burkina Faso: two phase 1, first-in-human trials. (PubMed, Lancet Microbe) - P1, P1/2 | "R21 with Matrix-M adjuvant has an acceptable safety profile. These data have formed the basis for efficacy testing of this vaccine."

Journal • P1 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Malaria • Rheumatology

R21 in Matrix-M adjuvant in UK malaria-naive adult men and non-pregnant women aged 18-45 years: an open-label, partially blinded, phase 1-2a controlled human malaria infection study. (PubMed, Lancet Microbe) - P1/2 | "Our study shows that R21/MM elicits high-level efficacy against clinical malaria in a controlled human infection model of malaria in adults who are malaria naive. These data supported the evaluation of R21/MM in field efficacy trials in the target population of young children in malaria-endemic areas."

Journal • P1/2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Malaria

Routine malaria vaccination in Africa: a step toward malaria eradication? (PubMed, Malar J) - "Recent progress has led to the approval of the first malaria vaccines, RTS,S/AS01 (Mosquirix®) and the R21/Matrix-M vaccine. Since the World Health Organization's endorsement of RTS,S in 2021 and R21 in 2023, several African countries, beginning with Cameroon, have integrated these vaccines into routine immunization programmes. This review examines the role of routine malaria vaccination in Africa as a key strategy toward malaria elimination, explores challenges and solutions for widespread vaccine implementation, and discusses future directions in the ongoing fight to eliminate malaria on the continent."

Journal • Review • Infectious Disease • Malaria

Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children. (PubMed, Lancet Infect Dis) - P2b | "RH5.1/Matrix-M appears safe and highly immunogenic in African children and shows promising efficacy against clinical malaria when given in a delayed third-dose regimen. This trial is ongoing to further monitor efficacy over time."

Journal • P2b data • Allergy • Immunology • Infectious Disease • Malaria

R21/Matrix-MTMphase III trial: further follow-up and assessment of an additional booster dose (ASTMH 2024) - "Further safety and efficacy data from the third year of follow-up will be presented, with the impact on vaccine efficacy of an additional booster dose following a third malaria season. These results all contribute to the growing body of data on R21/Matrix-M TM which will assist policy-makers in judging the optimal use of this low-cost, widely-accessible and high-impact vaccine."

P3 data • Infectious Disease • Malaria

IgG1 binding and IgG3 avidity associate with protection in R21/Matrix-M CHMI trials (ASTMH 2024) - P1/2 | "Sex was a significant contributor to most adjusted models; however, the only sex-specific difference observed in immune responses was significantly higher IgG1 NANP6 avidity in females (p = 0.046, Mann Whitney U test). Together, these results provide insight into how different R21/Matrix-M regimens influence immune responses and how those responses associate with protection from CHMI."

Late-breaking abstract • Infectious Disease • Malaria

Acceptability of malaria vaccination in areas with seasonal malaria transmission (ASTMH 2024) - "The WHO has recommended the use of the RTS,S/AS01 E and R21/Matrix-M malaria vaccines, including seasonal vaccination in areas with seasonal malaria transmission...However, participants across all groups stated that some caregivers would prefer malaria vaccine to SMC due to perceptions that the interventions act similarly and vaccines are more effective, issues with SMC side effects, and concerns of overdosing from taking both interventions. These findings can inform the introduction and implementation of malaria vaccines in areas with seasonal transmission, including co-implementation with SMC."

Late-breaking abstract • Infectious Disease • Malaria

Evaluation of a novel malaria vaccine candidate flCSP/SA-1 in comparison to RTS,S/AS01 in two pre-clinical models (ASTMH 2024) - "The World Health Organization (WHO) has recommended two pre-erythrocytic malaria vaccines, RTS,S/AS01 and R21/Matrix-M...Notably, the SA-1 adjuvant induced a longer IgG half-life than AS01 when formulated with flCSP in a non-human primate model. While further study is warranted, these data suggest that SA-1 could be an effective component of a next-generation malaria vaccine."

Late-breaking abstract • Preclinical • Infectious Disease • Malaria

Down-selection and manufacture of a next-generation epitope-based malaria vaccine candidate (ASTMH 2024) - "Implementation of the RTS,S/AS01E and R21/Matrix-M vaccines is poised to reduce childhood mortality in Africa...In head-to-head comparison, one of the major repeat constructs TMV-NPNAx20 adjuvanted with ALFQ, performed similar to RTS,S/AS01, at half the antibody concentration. Structural characterization, immunological optimization, and the low-cost manufacturing process of the TMV-NPNAx20/ALFQ vaccine will be discussed."

Late-breaking abstract • Infectious Disease • Malaria