RH5.1/Matrix-M / University of Oxford - LARVOL DELTA

Safety and immunogenicity of RH5.1 and R78C with Matrix-M®in UK adults in a Phase 1a trial - a novel combination vaccine candidate against the P. falciparum blood-stage RCR invasion complex demonstrates potent functional immunogenicity (ASTMH 2025) - "RH5.1/Matrix-M® (MM), a soluble protein vaccine targeting reticulocyte-binding protein homologue 5 (RH5), is the most advanced clinically, showing partial efficacy against clinical malaria in a Phase 2b trial...Immunogenicity data from this trial suggest that the combination of R78C and RH5.1 induces a superior antibody response as compared to leading blood-stage vaccine candidate RH5.1 alone and strongly support onward clinical testing. A Phase 1b trial of the combination vs. single components in Tanzania is ongoing."

Clinical • P1 data • Fatigue • Infectious Disease • Malaria • EGF

Superior functional humoral immunogenicity of blood-stage malaria vaccine candidates when given in a delayed third-dose (as compared to monthly) regimen and when targeting three proteins in the Plasmodium falciparum RH5-CyRPA-RIPR invasion complex . (ASTMH 2025) - P1 | "Furthermore, consistent with previous data from RH5.1/Matrix-M® alone trials, delayed third dose regimens (0,1,6 months) as compared to monthly dosing regimens (0,1,2 months) improve total IgG magnitude, avidity and durability. Analysis of antibody quantity versus GIA also indicates the relative quality of the vaccine-induced antibody response allowing assessment across all current blood-stage vaccine candidates in humans. These data are critical for the down-selection of the most promising blood-stage Pf vaccine candidates and regimens for future field efficacy assessment."

Infectious Disease • Malaria • EGF

Safety of and innate immune responses to the novel RH5.1/Matrix-M malaria vaccine in UK healthy adults (ASTMH 2025) - "By analysing the kinetics and nature of the innate immune activation, including the production of key cytokines and chemokines, we aim to identify potential correlates of both reactogenicity and the subsequent development of robust and durable antibody responses. Final immunogenicity data and exploratory analyses of cytokines and chemokines for associations with reactogenicity and antibody levels will be presented."

Clinical • Infectious Disease • Malaria

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

Safety and immunogenicity of a novel RH5.1/matrix-M malaria vaccine in UK healthy adults (ESCMID Global 2025) - No abstract available

Clinical • Infectious Disease • Malaria

A new RH5.1/Matrix-M candidate malaria vaccine: a promising finding to boost malaria elimination in Africa. (PubMed, Lancet Infect Dis) - No abstract available

Journal • 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

RH5.1/Matrix-M: highlighting blood-stage malaria vaccines. (PubMed, Lancet Infect Dis) - No abstract available

Journal • Infectious Disease • Malaria

Safety and Immunogenicity of RH5.1/Matrix-M in Adults and Infants Living in Tanzania (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: University of Oxford | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Malaria

RH5.1/Matrix-M™: Efficacy of a standalone blood-stage vaccine against clinical P. falciparum malaria in 5-17 month old children: a Phase 2b randomized trial in Burkina Faso (ASTMH 2024) - P2b | "Vaccine efficacy at 6 months as per the primary case definition was 55% (95% CI 20-75, P =0.007) in the delayed group and 40% (95% CI -0.03-65, P =0.065) in the monthly group. A 0-1-5-month regimen of RH5.1/Matrix-MTM appears safe, highly immunogenic, and shows the first promising efficacy of a RH5-based blood-stage vaccine when used alone, supporting further clinical development within a multi-stage vaccine strategy for Pf malaria."

Clinical • P2b data • Infectious Disease • Malaria

Characterization of the immune responses induced by the Plasmodium falciparum Blood-Stage Vaccine Candidate, RH5.1/Matrix M™, in a Phase IIb trial in Burkinabe 5-17month olds (ASTMH 2024) - P1, P2b | "A total of 360 5-17month olds were randomized to receive 3x 10 μg doses of RH5.1 with 50μg MM (2 groups of N=120 children, in a 0-1-2 month or a delayed 0-1-5 month regimen) or 3x doses of the rabies vaccine, Rabivax-S (2 groups of N=60 children, in a 0-1-2 or 0-1-5 month regimen). Type of vaccine delivery system, regimen and demographic characteristics of vaccinees have been shown to have substantial impact on anti-RH5 immune responses in studies to date. Here, we report the effects of monthly vs delayed third dose regimen on humoral response magnitude, quality and durability, as well as functional GIA assessment of antibody responses in the first opportunity for correlation with clinical malaria outcome for RH5-based vaccines."

P2b data • Infectious Disease • Malaria

Characterizing the Serological IgG Repertoire of Tanzanian Children Vaccinated with Novel Malaria Blood-Stage Candidate RH5.1/Matrix-M Adjuvant (ASTMH 2024) - P1 | "By cross-comparing the BCR- and Ig-Seq data sets, we determined the full-length VH and VL sequences of the most abundant circulating plasma IgG lineages in each individual child. The identified plasma lineages were subsequently expressed as recombinant monoclonal antibodies and functionally characterized for epitope specificity and in vitro parasite growth inhibition activity."

Clinical • Infectious Disease • Malaria

Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies. (PubMed, Cell Rep Med) - "These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials."

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

Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial. (PubMed, Lancet Infect Dis) - P1 | "The RH5.1/Matrix-M vaccine candidate shows an acceptable safety and reactogenicity profile in both adults and 5-17-month-old children residing in a malaria-endemic area, with all children in the delayed third dose regimen reaching a level of GIA previously associated with protective outcome against blood-stage P falciparum challenge in non-human primates. These data support onward efficacy assessment of this vaccine candidate against clinical malaria in young African children."

Journal • P1 data • Allergy • Immunology • Infectious Disease • Malaria • Pediatrics

Superior functional antibody activity of a delayed-boost vaccination regimen with the P. falciparum blood-stage vaccine RH5.1/Matrix-MTM in 5-17 month old Tanzanian infants (ASTMH 2023) - "These data suggest the importance of delayed rather than DFx dosing for RH5.1/MM in 5-17 month old infants. This delayed RH5.1/MM dosing regimen will now progress to a Phase IIb trial in 5-17 month old infants in Burkina Faso to assess efficacy against clinical malaria."

Infectious Disease • Malaria

Safety and Immunogenicity of RH5.1/Matrix-M in Adults and Infants Living in Tanzania (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: University of Oxford | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Malaria

Characterizing the effects of monthly versus delayed-boost vaccination regimens on humoral responses induced by the Plasmodium falciparum blood-stage vaccine RH5.1/Matrix-MTM in Tanzanian infants 5-17 months of age (ASTMH 2022) - "Consistent with the positive impact of delayed booster dosing on humoral immunity, RH5.1-specific long-lived plasma cells were detected in the bone marrow of vaccinated adults at a higher frequency in delayed versus monthly regimens. These data support the progression of RH5.1/Matrix-M candidate for 5-17 month old infants into Phase IIb efficacy trials against clinical malaria."

CNS Disorders • Infectious Disease • Malaria • Psychiatry • Schizophrenia

Safety and Immunogenicity of RH5.1/Matrix-M in Adults and Infants Living in Tanzania (clinicaltrials.gov) - P1; N=60; Enrolling by invitation; Sponsor: University of Oxford; Not yet recruiting ➔ Enrolling by invitation; Trial completion date: Nov 2022 ➔ Jul 2023; Trial primary completion date: Nov 2022 ➔ Jul 2023

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

Safety and Immunogenicity of RH5.1/Matrix-M in Adults and Infants Living in Tanzania (clinicaltrials.gov) - P1; N=60; Not yet recruiting; Sponsor: University of Oxford; Trial completion date: Apr 2022 ➔ Nov 2022; Initiation date: Apr 2020 ➔ Nov 2020; Trial primary completion date: Apr 2022 ➔ Nov 2022

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

Safety and Immunogenicity of RH5.1/Matrix-M in Adults and Infants Living in Tanzania (clinicaltrials.gov) - P1; N=60; Not yet recruiting; Sponsor: University of Oxford

Clinical • New P1 trial