CAPTIVATE · CorrelAtes of Protective immuniTy-driven Investigation of malaria VAccine combinaTion stratEgies

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.