Outer membrane vesicles as platform vaccine technology

Abstract

Outer membrane vesicles (OMVs) are released spontaneously during growth by many Gram‐negative bacteria. They present a range of surface antigens in a native conformation and have natural properties like immunogenicity, self‐adjuvation and uptake by immune cells which make them attractive for application as vaccines against pathogenic bacteria. In particular with Neisseria meningitidis, they have been investigated extensively and an OMV‐containing meningococcal vaccine has recently been approved by regulatory agencies. Genetic engineering of the OMV‐producing bacteria can be used to improve and expand their usefulness as vaccines. Recent work on meningitis B vaccines shows that OMVs can be modified, such as for lipopolysaccharide reactogenicity, to yield an OMV product that is safe and effective. The overexpression of crucial antigens or simultaneous expression of multiple antigenic variants as well as the expression of heterologous antigens enable expansion of their range of applications. In addition, modifications may increase the yield of OMV production and can be combined with specific production processes to obtain high amounts of well‐defined, stable and uniform OMV particle vaccine products. Further improvement can facilitate the development of OMVs as platform vaccine product for multiple applications.

Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion

“…Recent advances in bacterial engineering allow for the customization of OMVs (van der Pol et al, 2015). Strategies include the introduction of heterologous proteins in OMVs as well as retaining antigens which normally undergo proteolytic processing and are released from the bacterial membrane (Kuipers et al, 2015; van der Pol et al, 2015). The effectiveness of complement evasion molecules in vaccines is proven by N. meningitidis fHbp and B. pertussis FHA (Santolaya et al, 2012; Locht, 2016).…”

Membrane Vesicles Released by a hypervesiculating Escherichia coli Nissle 1917 tolR Mutant Are Highly Heterogeneous and Show Reduced Capacity for Epithelial Cell Interaction and Entry

“…Many studies with Gram-negative pathogens conducted in the last decade have shown that MVs are internalized in host cells and contribute to virulence by delivering cytotoxic factors as well as mediators that interfere with the immune system [4,5]. When first discovered, MVs from pathogenic bacteria were proposed as vaccines, and research in this field continues [6–8]. Promising novel therapy applications include using engineered MVs expressing antigens from pathogenic strains or as specialized drug delivery vehicles [9,10].…”

“…Hypervesiculating mutants can produce atypical MVs, which may have surface antigens with a different conformation or display altered immunogenicity, self-adjuvation, or uptake by host cells. The variability caused by these features can affect studies evaluating the application of MVs in different fields [8–10]. …”

Emerging Technologies for Low‐Cost, Rapid Vaccine Manufacture

“…Outer membrane vesicles (OMVs) are naturally generated by all gram‐negative bacteria during their growth . Gram‐positive bacteria, mycobacteria, and archaea can also naturally release OMVs.…”