ABSTRACT Although conventional vaccines and recent mRNA‐lipid nanoparticle platforms have revolutionized disease prevention, challenges remain regarding thermal stability, targeted delivery, and adverse immunogenic reactions. Exosomes, naturally occurring nanoscale extracellular vesicles (30–200 nm), have recently emerged as a highly innovative, biocompatible, and personalized platform for vaccine delivery. This comprehensive review systematically explores the latest advancements and structural innovations in exosome‐based vaccines. To highlight the innovation of these biological vectors, we categorize and critically evaluate exosomes based on their distinct cellular origins: Dendritic Cell‐derived exosomes (DEXs) possessing robust antigen‐presenting capabilities; Tumor‐derived exosomes (TDEs) harboring a rich repertoire of endogenous tumor antigens for cancer immunotherapy; and Plant‐derived exosome‐like nanovesicles (PELNVs) serving as an economical, highly scalable, and safe alternative vector. Furthermore, we provide a comparative analysis between exosome‐based platforms and traditional vaccines, emphasizing their superior capacity to cross biological barriers, facilitate direct or cross‐presentation of antigens, and elicit potent cellular and humoral immune responses. The therapeutic and prophylactic efficacies of these vaccines against various malignancies and severe infectious diseases (both viral, such as HIV, based on the “Trojan exosome” hypothesis, and non‐viral) are thoroughly discussed. Finally, we summarize ongoing clinical trials, critically assess potential biosafety risks (such as off‐target effects and oncogenic cargo transfer), and outline optimization strategies for large‐scale manufacturing. Ultimately, exosome‐based vaccines represent a paradigm shift in immunization, paving the way for next‐generation personalized medicine.
Kheirkhah et al. (Mon,) studied this question.