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Advancing vaccines with extracellular vesicles

Dr Christopher Locher, Versatope Therapeutics, explains why bacterial extracellular vesicles are ideally suited for recombinant vaccines because target antigens can be expressed as fusion proteins and targeted to the lumen, membrane or surface of the vesicles. These nano-size vesicles represent a potentially safe and simple subunit vaccine delivery platform that may increase the range of protection against diverse strains of infectious diseases and improve immune response to cancer-specific antigens, thereby reducing overall healthcare costs.

Exosomes, liposomes and lipid nanoparticles have long been used to deliver payloads effectively and thereby serve as extracellular transport vesicles (ETV). Bacterial extracellular vesicles (bEV) are nano-size lipid vesicles derived from bacteria that show much promise to revolutionise the biotechnology industry as ETVs.1 bEVs were first described by using electron microscopy of Vibrio cholerae, a Gram-negative bacterium, that causes outbreaks of severe intestinal diarrhoea and death in cases of acute dehydration.2 Although bEVs are derived from both Gram-positive and Gram-negative bacteria, it is the Gram-negative bacteria that are more frequently genetically manipulated, cloned and characterised for their outer membrane vesicles (OMVs). These vesicles bleb constitutively from the bacterial production cell and carry periplasmic and outer membrane components of signalling molecules, proteins, lipoproteins, nucleic acids, lipopolysaccharide and other polysaccharides that modulate bioactivity due to their ability to transport soluble and insoluble molecules.3 bEVs are thought to play a role in inter-bacterial communication, biofilm formation and quorum sensing as well as establishing an environmental niche through host cell modulation in the gut and throughout the body.4 This microbial communication using bEVs also occurs in plants, animals and marine environments.5-9 Furthermore, bEVs are associated with diverse diseases perhaps resulting from…