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

Public health impact of catch-up vaccination or additional booster doses with pre-erythrocytic malaria vaccine R21/Matrix-M: a modelling study. (PubMed, BMC Med) - "Catch-up campaigns or extra booster doses of R21/Matrix-M can provide benefits beyond routine administration, with the per-additional-dose value approaching that of routine vaccination, but this varies by transmission and seasonality setting. Further empirical studies, particularly on vaccine efficacy in older children, are warranted to inform policy guidance for malaria vaccination implementation."

Journal • Infectious Disease • Malaria

B and T cell responses to pre-erythrocytic R21/Matrix-M and blood-stage RH5.1/Matrix-M malaria vaccines in endemic settings. (PubMed, Front Immunol) - P1, P1/2, P1b | "Interestingly, while late time point anti-RH5.1 serum IgG concentrations in delayed booster children vaccinees matched previous reports with RH5.1/AS01B delayed fractional dosing in adults (NCT02927145; UK), IgG durability and relationship to RH5-specific B cells differed between these two cohorts. While our conclusions would be strengthened by further analyses in larger clinical trials, our data indicate that age, adjuvant dose, vaccine dose, and timing of final booster vaccination impact antigen-specific cellular responses to malaria vaccines and could thus inform the development of next-generation multi-stage malaria vaccination strategies."

Journal • Infectious Disease • Malaria • Pediatrics • CEBPZ

Suboptimal uptake of the malaria vaccine in Sudan: what's behind the blinds? (PubMed, Malar J) - "The suboptimal uptake of the malaria vaccine was not attributed to vaccine hesitancy or behavioral and social determinants, but rather to limited educational efforts and a lack of focus on the malaria vaccine as a new intervention. Reviewing the communication strategy and addressing health system barriers might help achieve the vaccine targets set by the Ministry of Health. Furthermore, assessing vaccine acceptability and identifying the enabling and inhibiting factors for vaccination before introducing the malaria vaccine in addition to engagement of higher authorities will lead to better vaccine uptake. Further research to test the effectiveness of culturally tailored communication interventions and the use of reminders or small incentives to raise the uptake is highly needed."

Journal • Infectious Disease • Malaria

Malaria immunity in the infant: progress and pitfalls. (PubMed, Curr Opin Immunol) - "The successful development and ongoing rollout of the first malaria vaccines, RTS,S/AS01E and R21/Matrix-M, have injected much-needed optimism into the malaria prevention field...Here, we review key aspects of the epidemiology and biology of P. falciparum infection in the fetus and infant, highlight recent findings regarding age-related differences in the immune response, and summarize current vaccination approaches in this vulnerable population. We discuss how emerging mechanistic insights might inform optimal deployment of existing preventive tools and guide development of next-generation strategies to protect infants from malaria."

Journal • Review • Infectious Disease • Malaria

Safety of Matrix-M-adjuvanted COVID-19, seasonal influenza, combination influenza-COVID-19, and malaria vaccines: a review of the evidence. (PubMed, Expert Rev Vaccines) - "Two authorized Matrix-M - adjuvanted vaccines, NUVAXOVID (COVID-19) and R21/Matrix-M (Plasmodium falciparum malaria), have been administered to >10 million people worldwide. Active-comparator clinical trials and post-marketing studies demonstrate favorable reactogenicity profiles of Matrix-M - adjuvanted vaccines compared with licensed vaccines for the same diseases, particularly, lower reactogenicity rates post - NUVAXOVID versus mRNA COVID-19 vaccination. Research is ongoing to better characterize Matrix-M immune-stimulating mechanisms, continue technology improvements, and identify new applications to enhance vaccines and therapeutics."

Journal • Review • Infectious Disease • Influenza • Malaria • Novel Coronavirus Disease • Respiratory Diseases

VAC087: A Study to Assess the Experimental Malaria Vaccines R78C and RH5.1 With Matrix-M in Combination With R21/Matrix-M (clinicaltrials.gov) - P2 | N=360 | Active, not recruiting | Sponsor: University of Oxford | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • 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 | Trial completion date: Jun 2025 ➔ Dec 2027 | Trial primary completion date: Jun 2025 ➔ Dec 2027

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

Knowledge, attitudes and factors associated with the awareness of caregivers of under-five children regarding the malaria vaccine in the Tiko Health District, Cameroon: A community-based cross-sectional study. (PubMed, PLOS Glob Public Health) - "The introduction of malaria vaccines, including RTS,S/AS01 (Mosquirix) and the recently WHO-recommended R21/Matrix-M, offers renewed hope for reducing malaria morbidity and mortality. Caregivers in the Tiko Health District exhibited limited knowledge and generally negative attitudes toward the malaria vaccine. Strengthening health-worker engagement, improving communication during routine immunization services, and addressing gaps in caregivers' understanding may enhance malaria vaccine uptake in the district."

Journal • Observational data • Infectious Disease • Malaria

The Evolving Landscape of Malaria Prevention Strategies: A Review of Recent Developments. (PubMed, Pathogens) - "Recent advances in vaccines, notably RTS,S/AS01 and R21/Matrix-M, represent landmark achievements, with large-scale rollouts demonstrating reductions in severe disease and mortality...However, challenges remain in ensuring equitable access, sustaining efficacy in the face of evolving parasite and vector biology, and integrating interventions into diverse health systems. This review highlights the need for adaptive, multifaceted approaches to achieve malaria elimination goals."

Journal • Review • Infectious Disease • Malaria

R21/Matrix-M in African Children Against Clinical Malaria (clinicaltrials.gov) - P3 | N=4800 | Active, not recruiting | Sponsor: University of Oxford | Trial completion date: Sep 2027 ➔ Apr 2028

Trial completion date • Infectious Disease • Malaria

Dose Finding Trial of R21/Matrix-M in School Children (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: University of Oxford | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2026 ➔ Mar 2027 | Initiation date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Jan 2026 ➔ Apr 2026

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Malaria

Assessment of Safety and Immunogenicity of R21/Matrix-M™ in African Children Living With HIV (clinicaltrials.gov) - P1 | N=122 | Completed | Sponsor: University of Oxford | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • Malaria

VINS: Effectiveness of Malaria Vaccines in Reducing the Risk of Invasive Non-typhoidal Salmonella Disease (clinicaltrials.gov) - P=N/A | N=10000 | Recruiting | Sponsor: International Vaccine Institute

New trial • Infectious Disease • Malaria

Dose-Escalating Study of Pfs230D1 in Combination With R21 in Matrix-M in African Adults (clinicaltrials.gov) - P1 | N=240 | Completed | Sponsor: Serum Institute of India Pvt. Ltd. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Malaria

Need for Real-World Evaluation of Malaria Vaccines and Reliable Vaccination Records in Africa. (PubMed, Am J Trop Med Hyg) - "However, both designs require accurate, individual-level vaccination data, which remains a major challenge in many African countries. Strengthening electronic immunization registries, alongside continued efforts to improve the quality and completeness of paper-based immunization records, is essential in African countries, not only for the evaluation of current vaccines such as RTS,S/AS01 and R21/Matrix-M, but also in preparation for future malaria vaccines, to support robust vaccine monitoring and decision-making."

HEOR • Journal • Real-world evidence • Infectious Disease • Malaria

Malaria: a review on its current epidemiological status and management strategies. (PubMed, Malar J) - "This includes cross-border prevention and control efforts, expansion of seasonal malaria chemoprevention programmes, identification of molecular markers of resistance, development of novel antimalarial agents, and scaled-up implementation of vaccines such as RTS,S/AS01 and R21/Matrix-M. Implementation of approaches employed by countries such as China in malaria elimination and strengthening global-Africa cooperation in the fight against malaria could further accelerate progress. This review aims to provide a comprehensive overview of global malaria with a focus on Africa and global efforts toward the continent's malaria elimination goals."

Journal • Review • Infectious Disease • Malaria

Determinants of caregivers' acceptance of the malaria vaccine: The case of Bamenda and Bamenda III Health Districts in Cameroon. (PubMed, Public Health Pract (Oxf)) - "Malaria continues to be a major health burden in sub-Saharan Africa, prompting the introduction of malaria vaccines such as RTS,S/AS01 (Mosquirix™) and R21/Matrix-M to reduce disease incidence. To improve vaccine uptake, targeted health communication strategies should focus on enhancing information accuracy, engaging trusted health professionals, and leveraging mobile health tools. Strengthening community engagement and addressing misconceptions are essential to achieving higher vaccine coverage and advancing malaria control efforts, especially in the Bamenda and Bamenda III Health Districts."

Journal • Infectious Disease • Malaria

L9LS-R21 Interaction (clinicaltrials.gov) - P2 | N=357 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Nov 2028 ➔ Mar 2029 | Initiation date: Nov 2025 ➔ Mar 2026 | Trial primary completion date: Nov 2027 ➔ Mar 2028

Trial completion date • Trial initiation date • Trial primary completion date • 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 completion date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Oct 2025 ➔ Feb 2026

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

VAC100: R21/MM Dosing, Presentations, and Preservatives (clinicaltrials.gov) - P4 | N=375 | Not yet recruiting | Sponsor: University of Oxford | Initiation date: Dec 2025 ➔ Mar 2026

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

Malaria vaccine protection against intradermal or venous parasites: a randomized phase 2b human challenge trial. (PubMed, Nat Med) - P2 | "Here, to test whether vaccine efficacy varies by route of inoculation, we undertook a phase 2b open, randomized controlled trial, recruiting healthy volunteers in Kenya for randomization to the circumsporozoite protein-based R21/Matrix-M vaccine (n = 38), thrombospondin-related adhesive protein fused to a multi-epitope string (ME-TRAP)-based vaccines (n = 24) or to control (n = 18)...Correlates of efficacy for antibodies to sporozoites should also be assessed by separate DVI and ID challenges. The study was registered with ClinicalTrials.gov ( NCT03947190 ) and PACTR ( PACTR202108505632810 )."

Journal • P2b data • Fatigue • Infectious Disease • Malaria • Pain

Systematic review of mHealth and digital health interventions to improve childhood vaccination uptake in 19 Sub-Saharan African countries. (PubMed, PLoS One) - "As 19 SSA countries were targeted to begin rolling out the two new malaria vaccines (RTS,S/AS01 and R21/Matrix-M) in 2024, this systematic review aims to investigate which mHealth/DH interventions are most effective at increasing vaccination uptake (by assessing vaccination coverage and timeliness outcomes) in these countries...The findings offer evidence-based insights to guide the development and implementation of mHealth/DH interventions within SSA childhood immunisation programmes. While interventions with voice-based components appear particularly promising, the limited certainty of evidence demonstrates further high-quality, context-specific research is required to draw stronger conclusions."

Journal • Review • Infectious Disease • Malaria • Pertussis • Respiratory Diseases • Tetanus

Preliminary insights into knowledge and attitudes toward malaria vaccination among Sudanese healthcare workers: an exploratory cross-sectional study. (PubMed, Malar J) - "The study highlights critical gaps in knowledge and predominantly unfavorable attitudes toward malaria vaccination among Sudanese HCWs, indicating a risk of vaccine hesitancy in frontline delivery. Targeted training and awareness programs are urgently needed to strengthen HCWs' capacity, dispel misconceptions, and build trust in the malaria vaccine as Sudan scales up immunization efforts."

Journal • Observational 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 | Recruiting | Sponsor: Epicentre | Not yet recruiting ➔ Recruiting

Enrollment open • Head-to-Head • Infectious Disease • Malaria

Molecular epidemiology of Plasmodium falciparum drug resistance and vaccine targets in high-transmission settings in Africa. (PubMed, Sci Rep) - "We identified high frequencies of dhfr-IRNI (90%) and dhps-SGKAA (45%) haplotypes, consistent with molecular markers of sulfadoxine-pyrimethamine (SP) resistance...The chloroquine-resistant Pfcrt-76T allele persisted at ~ 25% frequency, suggesting both sustained resistant lineages and a potential re-expansion of chloroquine-susceptible parasites...In parallel, polymorphisms within immunogenic domains of csp, the target of recently approved R21/Matrix-M vaccines were predicted to affect protein stability, though their functional consequences require experimental validation. Geographic analyses revealed localized clustering of resistance haplotypes, particularly in Kano and Yobe, reflecting heterogeneous selection pressures across transmission settings. Together, these findings establish a genomic surveillance framework for real-time monitoring of antimalarial resistance and vaccine-target polymorphisms in high-burden regions, with direct implications for evidence-based..."

Journal • Infectious Disease • Malaria • ABCB1 • DHFR