Engineered extracellular vesicles as a next-generation vaccine platform

Extracellular vesicles (EVs) offer a terrific arsenal for the design of next-generation nanovaccines, owing to several favorable features, such as excellent safety, immunostimulatory properties, lymphatic targeting ability, antigen-presentation capacity, facile modification characteristics, longer shelf-lives in vivo, and simpler good manufacturing practices handling procedures than cell-based vaccines. Here, we endeavor to summarize the state-of-the-art achievements in EV-based vaccines, particularly those aimed at immunizing against infectious pathogens and cancers. The emerging strategies for genetically or non-genetically engineering EVs to be loaded with antigenic proteins and antigen-encoding RNAs are highlighted. For each methodology, the rationale underlying its development is elaborated. In addition, EV biogenesis, cargo sorting, and immunomodulatory roles are discussed, as well as the clinical translation, latest industrial pipelines, current challenges, and envisioned directions for EV vaccines. This review may offer insights into the rational design of EVs as a cutting-edge vaccine platform to stimulate potent, broad, and long-lasting immunity.