Promising Extracellular Vesicle-Based Vaccines against Viruses, Including SARS-CoV-2

Sabanovic, Berina; Piva, Francesco; Cecati, Monia; Giulietti, Matteo

SIMPLE SUMMARY: Extracellular vesicles (EVs) allow cell-to-cell communication and can induce a strong immune response, by presenting antigens. EVs can be engineered to display viral antigens and so induce high and specific CD8(+) T cell and B cell reactions, highlighting these antigen-presenting EVs as a novel vaccine strategy. EVs present a low basal immunogenic profile and engineered EVs represent a safe, flexible, and efficient strategy for a virus-free vaccine design. Some biotech companies are developing EV-based vaccines against COVID-19, by displaying the SARS-CoV-2 Spike protein on the exosome surface or by delivering mRNAs of viral proteins through EVs. ABSTRACT: Extracellular vesicles (EVs) are secreted from almost all human cells and mediate intercellular communication by transferring heterogeneous molecules (i.e., DNA, RNAs, proteins, and lipids). In this way, EVs participate in various biological processes, including immune responses. Viruses can hijack EV biogenesis systems for their dissemination, while EVs from infected cells can transfer viral proteins to uninfected cells and to immune cells in order to mask the infection or to trigger a response. Several studies have highlighted the role of native or engineered EVs in the induction of B cell and CD8(+) T cell reactions against viral proteins, strongly suggesting these antigen-presenting EVs as a novel strategy for vaccine design, including the emerging COVID-19. EV-based vaccines overcome some limitations of conventional vaccines and introduce novel unique characteristics useful in vaccine design, including higher bio-safety and efficiency as antigen-presenting systems and as adjuvants. Here, we review the state-of-the-art for antiviral EV-based vaccines, including the ongoing projects of some biotech companies in the development of EV-based vaccines for SARS-CoV-2. Finally, we discuss the limits for further development of this promising class of therapeutic agents.