Update on Extracellular Vesicle-Based Vaccines and Therapeutics to Combat COVID-19

Abstract

The COVID-19 pandemic has had a deep impact on people worldwide since late 2019 when SARS-CoV-2 was first identified in Wuhan, China. In addition to its effect on public health, it has affected humans in various aspects of life, including social, economic, cultural, and political. It is also true that researchers have made vigorous efforts to overcome COVID-19 throughout the world, but they still have a long way to go. Accordingly, innumerable therapeutics and vaccine candidates have been studied for their efficacies and have been tried clinically in a very short span of time. For example, the versatility of extracellular vesicles, which are membrane-bound particles released from all types of cells, have recently been highlighted in terms of their effectiveness, biocompatibility, and safety in the fight against COVID-19. Thus, here, we tried to explain the use of extracellular vesicles as therapeutics and for the development of vaccines against COVID-19. Along with the mechanisms and a comprehensive background of their application in trapping the coronavirus or controlling the cytokine storm, we also discuss the obstacles to the clinical use of extracellular vesicles and how these could be resolved in the future.

Keywords: COVID-19; SARS-CoV-2; exosomes; extracellular vesicles; therapeutics; vaccine.

Figure 1

Schematic diagram displaying action mechanisms of EV-based therapeutics against COVID-19. SARS-CoV-2 enters and proliferates in the type 2 pneumocytes of the lung and then spreads into the interstitial tissue and bloodstream. Components of either viruses or dying cells activate alveolar macrophages and dendritic cells to recruit inflammatory cells to the lung tissue, resulting in the over-secretion of pro-inflammatory cytokines (cytokine storm). (1) EVs expressing ACE2-fused with CD9 (CD9-ACE2 EVs) or (2) palmitoylated ACE2 (palmitoylated ACE2 EVs) prohibit the binding of viruses to cellular ACE2. (3) EV-expressing RBDs of SARS-CoV-2 spike proteins fused with the stem region of the VSVG protein (VSVG-RBD EVs) target ACE2-expressing cells and thereby introduce anti-viral siRNAs to inhibit the proliferation of the viruses. (4) COVID-19-specific T-cell-derived exosomes (CSTS-Exo) show anti-viral effects on virus-infected cells by their cargo such as IFNγ. (5) EVs from mesenchymal stem cells (MSC-Exo) or (6) EVs expressing CD24 (CD24-EVs) can ameliorate the cytokine storm induced by over-activated inflammatory cells in the severe phase of COVID-19. The black lines briefly indicate the pathogenic pathways of SARS-CoV-2 infection in the airway, and the red lines denote the action mechanisms of the EV-based therapeutics interrupting the COVID-19 pathogenesis.