Outer Membrane Vesicle Induction and Isolation for Vaccine Development

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.

New strategy to select cross-reactivity Meningococci strains: immunization with Outer membrane vesicles of serogroup C and cationic lipid as adjuvant

“…The use of OMV in vaccines is well established against the serogroup B of N. meningitidis, since its capsular polysaccharide is poorly immunogenic and could induce autoimmunity [9]. OMV vaccines were used to control IMD outbreaks in Brazil, Cuba and New Zealand; the recombinant vaccine Bexsero (Glaxo Smith Kline) has been licensed in several countries and associates recombinant proteins with OMV from an epidemic N. meningitidis strain [23,24]. The protein nature of OMV makes them an interesting antigen to achieve efficient, long-term immunity,…”

“…Even though, it should be pointed that it was a preliminary study and the strain and antigenic preparation were obtained in laboratory-based conditions. Sometimes, the antigenic presentation of a bacterial strain can change when it goes to large-scale production, decreasing the immunogenic potential [24]. In this scenario, the importance of adjuvants to improve immunogenicity is restated.…”

Strategies to Tackle Antimicrobial Resistance: The Example of Escherichia coli and Pseudomonas aeruginosa

“…In the past years, outer membrane vesicles (OMV) have represented an attractive and cost-effective approach for vaccine development due to their built-in adjuvanticity, immunogenic properties and ability to induce humoral and cellular immune responses [ 32 , 36 ]. Moreover, the simultaneous presence and delivery of multiple antigens on OMV reduce the possibilities for the pathogen to generate vaccine escape mutants [ 29 ]. OMV first clinical use was to tackle Neisseria meningitidis outbreaks and from them three OMV-based vaccines (MenBvac, MeNZB and VA-MENGOCOC-BC) have been deployed to successfully fight meningococcal outbreaks [ 125 , 126 , 127 ].…”

“…The putative future impact that outer membrane vesicles (OMV) may have on both pathogens as tool for antigen discovery and as vaccine platform will also be discussed. OMV are indeed spherical particles derived from the outer membrane lipid bilayer of Gram-negative bacteria [ 29 ] ( Figure 1 ). They generally contain all surface antigens both protein or polysaccharide that in nature are on the surface of the bacterium and as such can provide a useful tool for both antigen discovery and delivery [ 30 ].…”

Outer Membrane Vesicles Protect Gram-Negative Bacteria against Host Defense Peptides

“…Modification of phospholipids happens in multiple species through a conserved protein, MprF, which adds a lysine to phosphatidylglycerol and thereby neutralizes the negative charge ( 18 ). Furthermore, it has been shown that addition of external membrane, in the form of outer membrane vesicles (OMVs) ( 19 ), protects Escherichia coli against polymyxin B and colistin, two peptide antibiotics ( 20 ). Similarly, addition of OMVs protected Helicobacter pylori against LL-37 ( 21 ).…”