Abstract
Gram-negative bacteria release vesicular structures from their outer membrane, so called outer membrane vesicles (OMVs). OMVs have a variety of functions such as waste disposal, communication, and antigen or toxin delivery. These vesicles are the promising structures for vaccine development since OMVs carry many surface antigens that are identical to the bacterial surface. However, isolation is often difficult and results in low yields. Several methods to enhance OMV yield exist, but these do affect the resulting OMVs. In this review, our current knowledge about OMVs will be presented. Different methods to induce OMVs will be reviewed and their advantages and disadvantages will be discussed. The effects of the induction and isolation methods used in several immunological studies on OMVs will be compared. Finally, the challenges for OMV-based vaccine development will be examined and one example of a successful OMV-based vaccine will be presented.
Highlights
ON OUTER MEMBRANE VESICLESGram-negative bacteria have two membranes, the inner membrane (IM) and the outer membrane (OM) with a network of peptidoglycan (PG) and the periplasmic space in between
Neisseria meningitidis outer membrane vesicles (OMVs) results are obtained in humans (Holst et al, 2009, 2013; Keiser et al, 2011), Bordetella pertussis OMV results are obtained from mice experiments (Roberts et al, 2008; Asensio et al, 2011; Raeven et al, 2016)
A synthetic anti-endotoxin peptide was shown to decrease E. coli OMV-induced activation of human macrophages (Pfalzgraff et al, 2019). These results indicate that antimicrobial peptides (AMPs) are the promising molecules for tailoring immune responses in vaccines, studies on other pathogens should reveal whether this mechanism is broadly applicable
Summary
Gram-negative bacteria have two membranes, the inner membrane (IM) and the outer membrane (OM) with a network of peptidoglycan (PG) and the periplasmic space in between. Both the IM and OM consist of phospholipids and membrane proteins, with only the outer leaflet of the OM containing lipopolysaccharide (LPS). Resulting OMVs are between 20 and 300 nm in diameter They consist of a single lipid bilayer containing LPS, phospholipids, and various outer membrane proteins (OMPs), which represents the OM of the originating bacteria. Formation of OMVs has been the subject of much debate, since the driving force of OMV formation was long unknown (Zhou et al, 1998; Haurat et al, 2011). The formation of OMVs was long thought to be an arbitrary stress response from bacterial cells (McBroom and Kuehn, 2007), but OMVs were later proven to have many more functions, which will be discussed below
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