A mechanistic framework for interpreting blood-stage malaria vaccine efficacy

Blood-stage vaccines (BSVs) against malaria offer a promising avenue for reducing parasite burden and transmission, yet their efficacy is challenging to interpret across different trial phases. In this study we develop a simple mechanistic within-host mathematical model of Plasmodium falciparum asexual parasitaemia. We fit this model to individual-level data from the phase I/IIa RH5.1 trial and estimate the relationship between vaccine efficacy and RH5 antibody titres, enabling the quantitative prediction of vaccine-impact on public health outcomes. We show that small reductions in erythrocyte invasion rate can lead to substantial decreases in probability of exceeding parasitaemia thresholds and transmission potential. Our framework provides a flexible, biologically motivated method for interpreting early-phase trial data and can inform future trial design, vaccine evaluation and integration into broader malaria control strategies.