28.06.2021: In a recently published proof-of-concept study, researchers from the University of Veterinary Medicine in Vienna were able to demonstrate that so-called bacterial vesicles can have applications in the development of more versatile and more efficient vaccines. According to the researchers, the approximately virus-sized bacterial products could, for example, serve as an adjuvant to create a stronger immune response in vaccines.

Bacteria release lipid-enclosed vesicles into the surrounding medium. These cell parts are known to be involved in many different cellular processes such as intercellular communication and waste disposal. Researchers from the Institute of Virology and the Institute of Immunology at Vetmeduni Vienna have now succeeded in positively exploiting (repurposing) these bacterial vesicles. By labelling these bacterial secretions with proteins from mammalian cells, they were able to generate more lifelike antigens. At the same time, the bacterial vesicles act as an immunologic adjuvant that triggers a stronger immune response. The result is a modular platform that could potentially enable a more targeted and faster development of vaccines.

The trick: hybrids on a bacterial basis

In their proof-of-concept study, the researchers from Vetmeduni Vienna, with the support of the Department of Pharmaceutical Sciences at the University of Vienna, examined the outer membrane vesicles (OMVs) of Escherichia coli (E. coli), bacteria that naturally occur in the intestines of healthy people. In their study, the researchers for the first time exploited a process already being successfully used by this working group in eukaryotic membranes. “By transferring the process of molecular painting or protein engineering to bacterial vesicles, we were able to generate a hybrid of perfectly eukaryotic proteins on a prokaryotic platform,” says first author Marianne Zaruba from the Institute of Virology at Vetmeduni Vienna.

Researchers harness bacterial secretions as platform for novel vaccine strategy

According to study director Christoph Metzner from the Institute of Virology at Vetmeduni Vienna, the E. coli vesicles have multiple benefits for novel vaccines: “The direct surface modification of outer membrane vesicles allows the deposition of eukaryotic proteins on a prokaryotic background. The immunostimulatory properties of the OMVs (e.g., B-cell stimulation) are not significantly changed. Parallel deposition of two different proteins is possible. In the development of novel vaccines, this would offer increased versatility and greater effectiveness against virus variants.” In addition to the fluorescent marker proteins used so far, cytokines, growth factors and antigens can also be transferred, generating a versatile modular platform for novel vaccine strategies.

Prokaryotic and eukaryotic bacteria produce similar products

Extracellular vesicles have recently attracted great attention, in part because of the emerging applications in gene therapy, vaccine production and diagnostics. Less well-known than their eukaryotic (organisms whose cells have a nucleus) counterparts, prokaryotic (unicellular organisms that lack a nucleus) bacteria also produce extracellular vesicles. In the case of E. coli, the main representatives are termed “outer membrane vesicles”.

The article “Surface Modification of E. coli Outer Membrane Vesicles with Glycosylphosphatidylinositol-Anchored Proteins: Generating Pro/Eukaryote Chimera Constructs” by Marianne Zaruba, Lena Roschitz, Haider Sami, Manfred Ogris, Wilhelm Gerner and Christoph Metzner was published in Membranes.