Title : Yeast-derived exosomes as a transformative platform for next-generation vaccine development
Abstract:
The persistent global demand for safer, more effective, and rapidly scalable vaccine platforms has driven innovations beyond traditional formulations. Exosomes, a class of nanosized extracellular vesicles (EVs), represent a revolutionary approach owing to their inherent biocompatibility, stability, and crucial role in intercellular communication. While the primary focus has been on exosomes derived from mammalian cells, exosomes released by yeast (YEVs) share fundamental characteristics with their mammalian counterparts, including a lipid bilayer and a similar size range of 25–250 nm, but exhibit unique advantages rooted in their host organism. The yeast cell wall contains powerful immunomodulatory components, such as β-glucan and mannoproteins, which are incorporated into YEVs. These components function as natural adjuvants, activating innate immune cells, such as macrophages and dendritic cells, and upregulating key maturation markers, such as CD40, CD80, and CD86. A recent study reported a 2-5-fold upregulation of these markers after exposure to YEVs, demonstrating their intrinsic adjuvanticity. This unique property can eliminate the need for separate immune- boosting additives, thereby streamlining vaccine design. This effect is mediated by the binding of yeast-derived β-glucans to Dectin-1 receptors on antigen-presenting cells, a well- characterized pattern recognition mechanism that triggers a potent downstream inflammatory and pro-immunogenic cascade. Furthermore, yeast's well-established industrial bioproduction infrastructure offers a clear pathway for scalable manufacturing, which is a critical bottleneck for other EV platforms. The ability to genetically engineer yeast to express and package specific vaccine antigens into YEVs further enhances the versatility and precision of this platform. Although challenges remain, particularly in standardizing isolation protocols and deciphering non-canonical biogenesis pathways in yeast, the synthesis of biological and industrial advantages positions YEVs as a highly promising avenue for developing effective, easily administered, and potent vaccines, particularly for oral delivery.
Keywords: Exosomes, Yeast, Vaccines, Extracellular vesicles, Adjuvants
