A Role for Extracellular Vesicles in SARS-CoV-2 Therapeutics and Prevention

Abstract

Extracellular vesicles (EVs) are the common designation for ectosomes, microparticles and microvesicles serving dominant roles in intercellular communication. Both viable and dying cells release EVs to the extracellular environment for transfer of cell, immune and infectious materials. Defined morphologically as lipid bi-layered structures EVs show molecular, biochemical, distribution, and entry mechanisms similar to viruses within cells and tissues. In recent years their functional capacities have been harnessed to deliver biomolecules and drugs and immunological agents to specific cells and organs of interest or disease. Interest in EVs as putative vaccines or drug delivery vehicles are substantial. The vesicles have properties of receptors nanoassembly on their surface. EVs can interact with specific immunocytes that include antigen presenting cells (dendritic cells and other mononuclear phagocytes) to elicit immune responses or affect tissue and cellular homeostasis or disease. Due to potential advantages like biocompatibility, biodegradation and efficient immune activation, EVs have gained attraction for the development of treatment or a vaccine system against the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection. In this review efforts to use EVs to contain SARS CoV-2 and affect the current viral pandemic are discussed. An emphasis is made on mesenchymal stem cell derived EVs' as a vaccine candidate delivery system.

Keywords: Coronavirus disease 2019 (COVID-19); Extracellular vesicles (EVs); Mesenchymal stem cells (MSCs); Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Fig. 1

EVs can facilitate antiviral immune responses. The exosome cargo consists of biomolecules including proteins, lipids, nucleic acids and metabolites. Each of these are either on the cell membrane or in an intravesicular compartment. Exosomes can interact with the immune cells, such as T-cells, NK-cells, macrophages, and dendritic cells, to modulate antiviral immune responses including against SARS-CoV-2. Exosomes can also exert “killing” effects on infected cells as well as delivery of viral pathogen-derived antigens. Exosomes, through loading therapeutic cargo, can be used for deployment of vaccines or therapeutic agents to generate robust antiviral immunity

Fig. 2

Approaches to use EVs for the treatment of COVID-19. MSCs induce immunoprotective and regenerative effects through EVs secretion. Therefore, EVs isolated from different source MSCs can directly affect the SARS-CoV-2. EVs also serve as natural carrier allow encapsulation of nucleic acids or small drug molecules for targeted delivery. Platelets were believed to induce exclusively proinflammatory responses. However, recent studies identified that EVs secreted from platelets exclusively exhibit anti-inflammatory and immunomodulating effects with ability to target inflammatory site. Convalescent plasma induced protective effects are attributed to neutralizing antibodies, growth factors and partially through their EVs. All these approaches can be used to target SARS-CoV-2 inflammatory sites and contain COVID-19