Extracellular vesicles as vaccine platforms: emerging opportunities for malaria

Malaria is the deadliest parasitic disease worldwide, and the urgent need for preventive strategies remains unmet. The parasite poses unique challenges, as it exhibits remarkable epitope variability and undergoes genetic mutations that allow adaptation to control measures, including drug treatment, and high ability of immune system evasion. In addition, malaria frequently develops asymptomatic forms, which sustain silent transmission and perpetuate the disease burden. In this complex context, extracellular vesicles (EVs) have emerged as promising tools for vaccine development. EVs can be engineered to carry specific and various antigens and to exploit their natural ability to fuse with cell membranes, enabling effective delivery. Depending on their cargo, they can modulate immune responses in a tailored manner, reawakening host immunity and targeting the parasite even in dormant stages. Despite extensive advances in EV-based approaches for viral and cancer models, their application to neglected diseases, including malaria, remains limited. This review aims to discuss strategies for engineering EVs as vaccines, drawing on insights from other disease models and highlighting the unique features of malaria that could benefit from such an approach.