Outer Membrane Vesicles: An Emerging Vaccine Platform

Abstract

Vaccine adjuvants are substances that improve the immune capacity of a recombinant vaccine to a great extent and have been in use since the early 1900s; they are primarily short-lived and initiate antigen activity, mainly an inflammatory response. With the developing technologies and innovation, early options such as alum were modified, yet the inorganic nature of major vaccine adjuvants caused several side effects. Outer membrane vesicles, which respond to the stressed environment, are small nano-sized particles secreted by gram-negative bacteria. The secretory nature of OMV gives us many benefits in terms of infection bioengineering. This article aims to provide a detailed overview of bacteria's outer membrane vesicles (OMV) and their potential usage as adjuvants in making OMV-based vaccines. The OMV adjuvant-based vaccines can be a great benefactor, and there are ongoing trials for formulating OMV adjuvant-based vaccines for SARS-CoV-2. This study emphasizes engineering the OMVs to develop better versions for safety purposes. This article will also provide a gist about the advantages and disadvantages of such vaccines, along with other aspects.

Keywords: adjuvants; outer membrane vesicles (OMV); vaccines.

Figure 1

A vaccine as therapeutic candidates from well-defined small pharmaceuticals protein to OMV and large undefined regenerative medicines.

Figure 2

Formation of OMVs. It shows loss or relocation of covalent linkages between the peptidoglycan layer and the outer membrane, peptidoglycan fragments and misfolded proteins protrude into the periplasmic space exerting a turgor pressure on the outer membrane leading to the OMVs pinch-ing off, and the enrichment of the curvature-inducing molecules such as B-band lipopolysaccharide and the quinolone PQS of Pseudomonas aeruginosa.

Figure 3

Helicobacter pylori Neutrophil Activating Proteins (HP-NAP) stimulates the release of Reactive Oxygen species (ROS), which damages the gastric epithelium. The delivery of HP-NAP through OMV to gastric mucosa thus increases the nutrient availability to bacteria via ROS-mediated mucosal damage. Gastric Epithelium Lining Figure Inspiration from [17].

Figure 4

Tailored OMV-based vaccine development against the MERS-CoV and H1N1.

Figure 5

Preparation and separation of OMVs.

Figure 6

Activation of cellular and humoral response through the OMVs. Legends: APC: Antigen Presenting Cells; PRR: Pathogen Recognition Receptor; TLR: Toll-like receptor; NLR: Nucleotide oligomerization domain (NOD)-like receptor; RLR: Retinoic acid-inducible gene I (RIG-I)-like receptor; IL: Interleukin; MHC: Major Histocompatibility Complex; TCR: T-cell receptor; Th: Helper T-cells; IFN: Interferon; CTL: Cytotoxic T lymphocytes; NK: Natural Killer.