Malaria remains a serious health concern worldwide, with P. falciparum considered one of the deadliest human parasites. Yet, the currently approved vaccine against malaria (RTS,S/AS01) offers limited protection due to challenges in vaccine development. Using current advances made in understanding immunity to address some of the existing challenges, this proposal aims to develop a more efficacious vaccine against P. falciparum by targeting multiple developmental stages (sporozoite, liver and blood-stage). In this project, combinations of 1) highly promising whole parasite vaccination approach targeting the liver (late-arresting GAP), 2) RTS,S (provided by GSK) and 3) mRNA versions of clinically evaluated and partially protective blood stage vaccine candidates (Rh5, AMA1-DiCo [sporozoite and blood stage]) will be evaluated in preclinical and small-scale human trials to discern the optimal combination for further clinical investigations. To inform a rational design of future vaccine candidates, CAPTIVATE will analyse the vaccine-induced immune response to acquire a full understanding of malaria protective immunity and develop an advanced immunology in-silico platform. While immunity to blood stage malaria is relatively well understood, the mechanisms of adaptive protective immunity for pre-erythrocytic malaria vaccine candidates are less well-established. CAPTIVATE addresses this critical knowledge gap by combining state-of-the-art preclinical and clinical (CHMI) in vivo malaria vaccine efficacy models with an innovative in-silico platform comprising TCR/VDJ sequencing and artificial intelligence predictions, to identify such mechanisms. CAPTIVATE assembles a unique combination of European experts in their respective fields (malaria modelling in primates, clinical vaccine testing, in-silico modelling of immune responses, innovative omics approaches) in an integrated interdisciplinary approach aimed at bringing the next generation malaria vaccines to the clinic.
Metabolomics, lipidomics, and proteomics technologies will enable more comprehensive approach to biomarker discovery and the elucidation of malaria immune system mechanisms, understanding of the molecular pathways underlying protective adaptive immune responses to malaria vaccines.
By enabling more effective vaccination strategies, CAPTIVATE contributes to the long-term goal of reducing malaria’s global burden. Additionally, it strengthens healthcare systems through enhanced scientific capability and informs broader public health decision-making through improved understanding of immune protection. The outcomes are expected to benefit patients, healthcare providers, and policymakers by reducing disease risk and enhancing resilience against communicable diseases.
