Mosquirix (RTS,S) / GSK - LARVOL DELTA

Safety of RTS,S/AS01E malaria vaccine up to 1 year after the third dose in Ghana, Kenya, and Malawi (EPI-MAL-003): a phase 4 cohort event monitoring study. (PubMed, Lancet Glob Health) - P | "We found no evidence of vaccination being associated with an increased risk of meningitis, cerebral malaria, or mortality among vaccinated children, and no new safety risks were identified."

Journal • P4 data • CNS Disorders • Epilepsy • Epstein-Barr Virus Infections • Infectious Disease • Malaria • Pneumococcal Infections • Pneumonia

Incidence rates of malaria, meningitis, and mortality in children younger than 5 years: a prospective cohort study in Ghana and Kenya before the roll-out of the RTS,S/AS01E malaria vaccine from 2016 to 2022. (PubMed, Lancet Glob Health) - "Observed incidence of meningitis and cerebral malaria were in the previously published range, whereas childhood mortality was lower, suggesting that the recent efforts to reduce mortality in children younger than 5 years have been impactful. Data from this study have public health use and will form the baseline evidence for ongoing evaluation of the benefit-risk of RTS,S/AS01E."

Journal • CNS Disorders • Infectious Disease • Malaria

The effect of disease transmission on time-aggregated treatment efficacy estimates: a critical analysis of factors influencing the RTS,S and R21 malaria vaccine phase 3 trials. (PubMed, Lancet Infect Dis) - "Using published results from R21 and RTS,S trials, we show this effect and provide a series of counterfactual predictions, illustrating how vaccine efficacy might differ, by between 10% and 20% in some cases, under alternative vaccination dates. We also discuss how this effect might confound efforts to identify determinants of protective efficacy and offer recommendations to address it in the analysis and reporting of trial results."

Journal • P3 data • Review • Infectious Disease • Malaria • Pediatrics

Identification of a Protective Non-CSP Epitope for Enhanced Malaria Vaccine Strategies (IMMUNOLOGY 2025) - "Notably, 14G3 reduced sporozoite invasion and delayed parasitemia in a mouse model. This protective non-CSP epitope is a promising candidate for combination vaccine strategies against malaria."

Infectious Disease • Malaria

Development of Malaria Vaccines Using the Sail eRNATM Platform (IMMUNOLOGY 2025) - "eRNA performance was confirmed in a malaria vaccine reference laboratory where anti-PfCSP antibody titers were significantly greater for four of the five R21 eRNA vaccines than those reported for licensed malaria vaccines. These results demonstrate the potential of Sail’s eRNA platform to generate a scalable vaccine for malaria, with superior efficacy and durability than first-generation vaccines."

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."

Infectious Disease • Malaria • CD4 • ZEB2

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

A roadmap of priority evidence gaps for the co-implementation of malaria vaccines and perennial malaria chemoprevention. (PubMed, Malar J) - "Together, these areas will provide practical guidance on the co-implementation of the interventions, and robust evidence to inform decision-making on how best to design, optimize and scale-up co-implementation in different contexts, including if and in what contexts the co-implementation is cost-effective, and the optimal schedule for co-implementation. This will work towards supporting the policy process on co-implementation of malaria vaccines and PMC, and achieving the most impactful use of available resources for the prevention of malaria in children."

Journal • 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

Enhancing malaria elimination in high-transmission settings: the synergy of concurrent vector control and chemotherapy. (PubMed, Malar J) - "Synergistic intervention effects are crucial, but implementation context is paramount. While combining malaria interventions can be highly effective, not all combinations yield equal results. Thus, tailoring strategies to the specific local context and transmission dynamics is essential for maximizing impact. Moreover, successful malaria elimination is heavily reliant robust health systems and understanding the biological and operational challenges. Consequently, adaptable, evidence-based strategies are required to overcome these obstacles and achieve lasting progress toward malaria elimination."

Journal • Review • 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

Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection. (PubMed, Malar J) - P1 | "The two-dose priming immunization regimen was safe, well tolerated and highly immunogenic. Larger studies may better define the adverse event profile of condensed regimens of PfSPZ Vaccine in malaria-naive adults."

Clinical • Journal • Fatigue • Infectious Disease • Malaria • Musculoskeletal Pain • Pain

Early Activation of Lung CD8+ T Cells After Immunization with Live Plasmodium berghei Malaria Sporozoites. (PubMed, Pathog Immun) - "These differences start already at the early 2-day timepoint at which time the lungs show an impressive 10.2% increase in TNF+ CD8+ T cells, whereas the liver shows a more modest increase of 2.6% of these cells. These findings highlight the lungs as a crucial site for immune priming and T-cell activation, underscoring the need for further investigation of organ-specific responses to fully understand the potential of LA-GAP immunization as a powerful strategy in the fight against malaria."

Journal • Infectious Disease • Malaria • CD8 • GZMA • ITGAX • KLRG1

Computational Development of Transmission-Blocking Vaccine Candidates Based on Fused Antigens of Pre- and Post-fertilization Gametocytes Against Plasmodium falciparum. (PubMed, Bioinform Biol Insights) - "The low-binding interaction energy that resulted from molecular docking and dynamics simulations showed a strong affinity of FAVCs to Toll-like receptor 5 (TLR5). The results indicate that the FAVC-FSE vaccine candidate is more promising to interrupt P falciparum transmission and provides a baseline for experimental validation."

IO biomarker • Journal • Cholera • Infectious Disease • Malaria • CD4 • CD8 • TLR5

MVPE-CC: Strengthening the Evidence for Policy on the RTS,S/AS01 Malaria Vaccine (clinicaltrials.gov) - P=N/A | N=9280 | Recruiting | Sponsor: Kintampo Health Research Centre, Ghana | Active, not recruiting ➔ Recruiting | Trial completion date: Jun 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2023 ➔ Apr 2025

Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease • Malaria • Mood Disorders

iDC-targeting PfCSP mRNA vaccine confers superior protection against Plasmodium compared to conventional mRNA. (PubMed, NPJ Vaccines) - "Importantly, upon P. berghei PfCSP transgenic sporozoite challenge, MIP3α-CSP mRNA provided significantly greater protection from liver infection, strongly associated with multifunctional CD4 + T cells and anti-NANP6 titers. This study underscores iDC targeting as a promising strategy to enhance malaria vaccine efficacy."

Journal • Hepatology • Infectious Disease • Malaria • Novel Coronavirus Disease • CD4

Where is the hard-to-reach population? Spatial analysis from a cross-sectional study on the access to bed net and malaria vaccine in the Lake Victoria Region, Kenya. (PubMed, Malar J) - "Uptake of LLIN and malaria vaccine in Homa Bay County, Kenya varied by geography and household characteristics. These findings suggest that different sets of actions should be considered to improve the coverage and compliance of these interventions in different areas."

Journal • Observational data • 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

The anti-circumsporozoite antibody response to repeated, seasonal booster doses of the malaria vaccine RTS,S/AS01E. (PubMed, NPJ Vaccines) - P3 | "Although anti-CSP antibody titres declined after repeated booster doses of RTS,S/AS01E a high, although declining, level of efficacy was sustained suggesting that there may have been changes in the characteristics of the anti-CSP antibody following repeated booster doses.Clinical Trials Registration. NCT03143218."

Journal • Infectious Disease • Malaria

Genetic diversity of Plasmodium falciparum reticulocyte binding protein homologue-5, which is a potential malaria vaccine candidate: baseline data from areas of varying malaria endemicity in Mainland Tanzania. (PubMed, Malar J) - "Low levels of polymorphism in the pfrh5 gene were observed based on low nucleotide and haplotype diversity, a lack of population structure and negative Tajima's D values. This study provides essential data on the diversity of the Pfrh5 gene indicating that it can be considered in the development of the next generation malaria vaccines. Robust and intensive studies of this and other candidate genes are crucial to support the prioritization of the Pfrh5 gene for potential inclusion in a broadly cross-protective malaria vaccine."

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

Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya. (PubMed, Front Parasitol) - "When assessing the predicted binding affinities between supertypes in HLA class I and II with the identified haplotypes, we observed stronger predicted binding affinities to multiple haplotypes except for those containing the 3D7 reference. The results suggest the need to take into account the existing changes occurring in Pfcsp while developing malaria vaccines."

Journal • Infectious Disease • 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

Influence of trust on the acceptance of the RTS,S malaria vaccine in the Kassena-Nankana districts of Ghana. (PubMed, Malar J) - "The results of this study suggest that trust in the malaria vaccine is critical for its uptake. Therefore, efforts towards improving acceptance of the vaccine should be focused on building and sustaining trust for the vaccine among mothers and community members."

Journal • Ebola Virus Disease • Infectious Disease • Malaria