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

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

Modelling the impact of different intervention packages for malaria control under varying intensities of pyrethroid resistance. (PubMed, Malar J) - "Compared to ITNs alone, combining ITNs with IRS and/or biolarvicides greatly improves malaria control at low to moderate intensities of pyrethroid resistance but yields no additional benefits at high resistance intensities. However, integrating these vector control strategies with immunization and effective case management using artemisinin-based combination therapy (ACT) further enhances impact by reducing both parasite transmission and the infectious reservoir."

Journal • Infectious Disease • Malaria

Awareness, acceptability, and willingness to pay for the R21/Matrix-M malaria vaccine: a cross-sectional study among pregnant women and nursing mothers in Enugu State, Nigeria. (PubMed, BMC Public Health) - No abstract available

Journal • Observational data • Infectious Disease • Malaria

mRNA delivery of circumsporozoite protein epitope-based malaria vaccines induces protection in a mouse model. (PubMed, NPJ Vaccines) - "The licensed malaria vaccines (RTS,S/AS01 and R21/Matrix-M) have shown significant efficacy in human phase 3 trials...mRNA-delivered nanoparticle and membrane-anchored immunogens displaying both the junctional and NANP repeat epitopes were most effective, exhibiting 99% reduction in liver burden and sterilizing immunity from parasitemia in some mice. The mRNA immunogens represent promising candidates for rapid translation to human challenge studies and could be combined with T cell vaccines to comprise a potential next-generation malaria vaccine."

Journal • Preclinical • Infectious Disease • Malaria

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 | Recruiting | Sponsor: University of Oxford | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Malaria

A Phase 1 Study to Assess an Escalating Dose, Multi-prime Vaccination Schedule of R21/Matrix-M™ (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: University of Oxford | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Malaria

Targeted Sequencing Identifies SNPs Associated with Antimalarial Drug Resistance and the CSP Vaccine Antigen in Plasmodium falciparum from Southwest Cameroon. (PubMed, Int J Mol Sci) - "In parallel, the recent rollout of the RTS,S/AS01 and R21/Matrix-M malaria vaccine-targeting the Plasmodium falciparum circumsporozoite protein (CSP)-offers a new prevention tool but may be influenced by parasite genetic diversity...Nineteen non-synonymous SNPs were identified in pfcsp, reflecting natural background variations as vaccination status was not known. These findings support the continued use of artemisinin-based combination therapies and underscores the need for sustained molecular surveillance of both antimalarial drug resistance and vaccine-related polymorphisms, to inform malaria control strategies."

Journal • Infectious Disease • Malaria • ABCB1

Full-length merozoite surface protein 1 formulated with GLA-SE adjuvant in malaria pre-exposed adults: a randomised, controlled, double-blind, parallel-group, single-centre Phase Ib trial. (PubMed, EClinicalMedicine) - P1 | "A highly effective blood-stage malaria vaccine targeting the merozoite surface protein 1 (MSP1) of Plasmodium falciparum (Pf) might complement the imperfect protection conferred by the currently available first-generation pre-erythrocytic malaria vaccines RTS,S/AS01E and R21/Matrix-M...SUM-101 elicited robust MSP1-specific IgM and IgG antibody titers, with peak levels observed on day 56 and day 84, respectively...KG by the EU Malaria Fund Berlin GmbH & Co. KG."

Journal • P1 data • Fatigue • Hematological Disorders • Infectious Disease • Malaria • Pain

Repertoire, function, and structure of serological antibodies induced by the R21/Matrix-M malaria vaccine (ASTMH 2025) - "Monoclonal antibodies derived from these NANP-specific IGHV3-30/3-33 lineages effectively blocked sporozoite invasion in vitro and conferred protection against parasitemia in vivo. Together, these findings demonstrate that R21/Matrix-M induces focused, low-mutation polyclonal IgG responses capable of recognizing multiple protective CSP determinants, shedding light on the molecular basis of its demonstrated protective efficacy against P. falciparum."

Late-breaking abstract • Infectious Disease • Malaria

Immunological and functional characteristics of a coformulated conjugated Pfs230D1+R21/Matrix-M vaccine in non-human primates (ASTMH 2025) - P1 | "On day 1, a small but significant fraction of differentially expressed genes were shared between Pfs230D1-CRM197, R21 and Pfs230D1-CRM197 + R21 (pairs ranging from 16.1% to 23.7%). Overall, our findings support further clinical development of a co-formulated Pfs230D1-CRM197+R21/MM1 vaccine and draw attention to possible vaccine interference."

Late-breaking abstract • Infectious Disease • Malaria

De novo design and experimental characterization of germline targeting vaccines against Plasmodium falciparum circumsporozoite protein (CSP) repeats (ASTMH 2025) - "Currently licensed pre-erythrocytic vaccines, RTS,S/AS01 and R21/Matrix-M, target the P. falciparum circumsporozoite protein (CSP) but exhibit limited durability and quality of antibody responses, potentially due to the exclusion of protective junctional (NPDP) and minor (NVDP) repeat epitopes. Clinical trials with NPDP-targeting CIS43LS and NVDP-targeting L9LS mAbs have demonstrated significant efficacy, validating these epitopes as vaccine targets...Moreover, L9 immunogens successfully recruited germline-L9 B cells to germinal centers, and cryo-EM structures confirmed precise scaffolding of L9 Fab-Fab complexes. These findings underscore the potential of deep learning-enabled protein design to develop next-generation malaria vaccines that elicit potent, conformation-specific protective antibody responses."

Late-breaking abstract • Infectious Disease • Malaria

Comparison of current four-dose schedule versus expanded three-dose schedule of RTS,S/AS01 and R21/Matrix-M malaria vaccines: a modelling study. (ASTMH 2025) - "Comparing the two strategies using an equivalence analysis with a 5% effect threshold, we found that in most cases (except for allocation to much lower transmission), reallocation is neither inferior nor superior to the existing four-dose strategy. Overall, if the fourth dose is reallocated to extend the three-dose primary series to more children, the impact on total population disease burden averted remains similar and is neither better nor worse than the current four-dose schedule."

Late-breaking abstract • Infectious Disease • Malaria

A new platform for the study of Plasmodium falciparum sporozoites from natural infections (ASTMH 2025) - "Indeed, the two available malaria vaccines, RTS, S/A01 and R21/Matrix-M, are designed to interfere with the ability of sporozoites to invade hepatocytes successfully...Both infected mosquitoes and P. vivax sporozoites have been shipped around the globe for CHMIs and for in vitro studies of hepatocyte stages. This new platform at CERMEL opens unique opportunities for international collaborators to investigate for the first time the infection biology, protective efficacy or experimental drugs and vaccines, and the pre-erythrocytic biology of Plasmodium falciparum representative of natural, genetically diverse parasite populations."

Late-breaking abstract • Infectious Disease • Malaria

Scalable in vitro production of Plasmodium falciparum sporozoites using a 3D culture system for vaccine development. (ASTMH 2025) - "While current vaccines such as RTS,S and R21/Matrix-M represent considerable progress, they offer only partial and short-lived protection...Functional validation confirmed that IVS maintain key biological properties: they exhibit gliding motility, infect HC-04 hepatocytes in vitro, and complete liver-stage development in FRG huHep mice, progressing to blood stage. This next-generation IVS platform enables large-scale SPZ production for use in live attenuated vaccine pipelines and opens new avenues for translational research and preclinical testing of malaria interventions."

Late-breaking abstract • Preclinical • Infectious Disease • Malaria

Modelling the potential public health impact of blood-stage malaria vaccines alone and in combination (ASTMH 2025) - "Simulations assessed the impact of a vaccine deployment under various strategies: as a standalone intervention in addition to the current standard of care, and as a combination strategy with the pre-erythrocytic vaccine R21/Matrix-M...As clinical testing of leading BSV candidates and combination vaccines proceeds, this modelling study adds supportive understandings of the potential impact of these vaccines at population level, including the potential additive or synergistic benefits of combination vaccine antigens on severe disease. These findings offer support for investment decisions, product development, clinical trial design, and policy decision-making, helping to prioritize the development of BSV candidates with the highest potential for public health benefit."

Late-breaking abstract • Infectious Disease • Malaria

Characterisation of the immune responses induced by the blood-stage vaccine candidate RH5.2/Matrix-M® alone and in combination with the licensed pre-erythrocytic vaccine R21/Matrix-M®. (ASTMH 2025) - P1 | "Here in a Phase Ib (NCT05357560) clinical trial, administering RH5.2-VLP alone and in combination with R21 formulated in MM in Gambian adults and children, as a multi-stage malaria vaccine candidate, we report vaccine immunogenicity, assessing antibody magnitude over time as well as functional GIA. Antibodies to blood-stage component of this study were assessed against both full-length RH5 immunogen (RH5.1) and RH5.2 vaccine immunogen to allow correlation with GIA outcome. This is the first opportunity for analysis of humoral immunogenicity of an RH5-based vaccine in the context of a multi-stage regimen, and for comparison between second generation RH5.2 and previously reported data with the more advanced RH5.1/MM candidate, critical for blood-stage vaccine candidate down selection and multi-stage vaccine development."

Combination therapy • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Malaria

Design of a Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effect of the Anti-sporozoite Monoclonal Antibody L9LS on R21/Matrix-MTM Vaccine Immunogenicity (ASTMH 2025) - "A high priority potential use case for L9LS is malaria prevention in infants before they complete the 3-dose series of RTS,S/AS01 (RTS,S) or R21/Matrix-M™ (R21) at 7-9 months of age...Primary study objectives include evaluation of the safety and tolerability of L9LS and R21 when administered in close succession, as well as R21 immunogenicity (total IgG anti-NANP titers) at 28 and 84 days following the 3rd and 4th dose of R21. Additional study evaluations include L9LS pharmacokinetics, anti-drug antibody assessments, and Pf infection and clinical malaria risk."

Clinical • P2 data • Infectious Disease • Malaria

Towards a low cost, cold chain-independent and needle-free seasonal booster for sustaining malaria immunity (ASTMH 2025) - "First-generation malaria vaccines RTS,S/AS01 and R21/Matrix-M contain a chemically adjuvanted antigen derived from the malaria circumsporozoite protein displayed on the surface of a virus like particle (VLP) assembled by a recombinant hepatitis B capsid antigen...Current efforts focus on developing GMP material and initiating first-in-human clinical trials. Supportive preclinical data will be presented to demonstrate the feasibility and immunological potential of this approach for seasonal deployment in malaria-endemic regions."

Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Malaria

Duration of protection and cost-effectiveness of malaria vaccine candidate R21/Matrix-M: a modelling study applied to phase 3 clinical trial data (ASTMH 2025) - "To increase certainty in the long-term protection against infection provided by R21/Matrix-M, additional long follow-up trial data beyond 30 months is required. Overall, the expected impact of R21/Matrix-M supports country level decisions to implement the vaccine as part of their malaria control strategy."

Clinical • Cost effectiveness • HEOR • P3 data • Infectious Disease • Malaria

R21/Matrix-M™ malaria vaccine: Three-year efficacy and safety results from a phase III clinical trial (ASTMH 2025) - "Further safety and efficacy data over 3 years from all sites and 3.5 years in seasonal sites will also be presented. R21/Matrix-M™'s sustained, equitable, and high-level effectiveness, along with a commitment to affordable, large-scale supply, promises meaningful short- and long-term benefits for people in malaria-endemic regions."

Clinical • P3 data • CNS Disorders • Epilepsy • Infectious Disease • Malaria

A Phase Ib trial to assess the safety and tolerability of the blood-stage malaria vaccine candidate RH5.2 virus-like particle (VLP) in Matrix-M™ and the pre-erythrocytic stage vaccine R21 in Matrix-M™, both alone and in combination, in adults . (ASTMH 2025) - "Current WHO-approved malaria vaccines are only effective against the pre-erythrocytic stage of malaria. RH5.2-VLP/Matrix-M™, given alone or combined with R21, had a favorable safety profile and was well tolerated. These results pave the way for further studies to assess vaccine immunogenicity."

Clinical • P1 data • Anorexia • Fatigue • Infectious Disease • Malaria • Respiratory Diseases

Safety and immunogenicity of delayed third dose of R21/Matrix-M malaria vaccine in children in Mali (ASTMH 2025) - "Both vaccine schedules were safe with no grade 3 or serious adverse events related to vaccination. Analysis of immunogenicity is ongoing, and results will be presented."

Clinical • Infectious Disease • Malaria

Comparative immunogenicity of two pre-erythrocytic malaria vaccines: RTS,S and R21 (ASTMH 2025) - P1/2, P3 | "RTS,S/AS01 (RTS,S) and R21/Matrix-M (R21) vaccines have been rolled out for children aged 5-36 months at risk of malaria across Africa, despite RTS,S only having been tested in 5-17-month-olds...Levels of IgG against HBsAg were higher in individuals vaccinated with RTS,S than with R21 at all timepoints after vaccination. We observed no difference in immunogenicity between age groups when 5-11 months and 12-17 month-olds were analysed separately."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • Malaria

Acceptability, Knowledge, Attitudes and Practices on Malaria Vaccination Among Caregivers in Liberia (ASTMH 2025) - "WHO recommends the use of the RTS,S/AS01 (or RTS,S) and R21/Matrix-M vaccines to reduce malariamorbidity and mortality in children living in areas with moderate to high P. falciparum malariatransmission...Timely reminders directed to caregivers before each dose will address gaps inknowledge. In parallel, reinforcing health worker training, enhancing defaulter tracking, and conductingtargeted evaluations will be essential to improve uptake."

Infectious Disease • Malaria

Safety and immunogenicity of the malaria vaccine candidate R21/Matrix-MTM when co-administered with EPI vaccines at 6, 10 and 14 weeks of age in Malian children (ASTMH 2025) - "Antibody responses to R21/Matrix-M were lower in this age group, as expected, and responses to each EPI vaccine administered with or without R21/Matrix-M were largely unaffected: data will be presented. These data show that R21/Matrix-M is safe when administered together with early childhood vaccines in young infants but induces reduced immune responses."

Clinical • Infectious Disease • Malaria • Pneumococcal Infections • Rotavirus Infections