OMV Vaccines and the Role of TLR Agonists in Immune Response.

Francesca Mancini,Francesca Necchi,Francesca Micoli,Omar Rossi

doi:10.3390/ijms21124416

Francesca Mancini, Francesca Necchi + Show 2 more

Open Access

https://doi.org/10.3390/ijms21124416

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Abstract

Outer Membrane Vesicles (OMVs) are bacterial nanoparticles that are spontaneously released during growth both in vitro and in vivo by Gram-negative bacteria. They are spherical, bilayered membrane nanostructures that contain many components found within the external surface of the parent bacterium. Naturally, OMVs serve the bacteria as a mechanism to deliver DNA, RNA, proteins, and toxins, as well as to promote biofilm formation and remodel the outer membrane during growth. On the other hand, as OMVs possess the optimal size to be uptaken by immune cells, and present a range of surface-exposed antigens in native conformation and Toll-like receptor (TLR) activating components, they represent an attractive and powerful vaccine platform able to induce both humoral and cell-mediated immune responses. This work reviews the TLR-agonists expressed on OMVs and their capability to trigger individual TLRs expressed on different cell types of the immune system, and then focuses on their impact on the immune responses elicited by OMVs compared to traditional vaccines.

Highlights

Outer Membrane Vesicles (OMVs) are 25–250 nm round shaped exosomes that are spontaneously released during growth by both pathogenic and nonpathogenic Gram-negative bacteria, especially during the end of log phase growth and at sites of cell division [1].One of the first reports on outer membrane vesicle (OMV) produced during the growth of Escherichia coli cells was published nearly 40 years ago by Wensink and Witholt [2] and indicated an imbalance of lipoproteins in OMVs versus outer membranes
We focus our attention on dissecting the roles of PAMPs and Toll-like receptor (TLR) agonists associated with OMVs and their impact on immune responses elicited by OMV-based vaccines
The affinity of the specific interaction between each TLR and its ligand starts from nanomolar concentrations of PAMPs, as in the case of TLR2, 3, 5, and 9 [60,65,66], or from higher ligand concentration, as for TLR4 [64], and it is different in different cells

Summary

Introduction

Outer Membrane Vesicles (OMVs) are 25–250 nm round shaped exosomes that are spontaneously released during growth by both pathogenic and nonpathogenic Gram-negative bacteria, especially during the end of log phase growth and at sites of cell division [1]. The potential for inducing a strong immune response together with the simplicity of manufacture, have made OMVs an attractive platform for vaccine development To this end, genetic manipulations have been introduced in bacteria to further enhance the in vitro blebbing, by the disruption of genes involved in processes including the synthesis of proteins linking the outer membrane and the underlying peptidoglycan layer, envelope structure, and cellular stress [31,32,33]. Genetic manipulations have been introduced in bacteria to further enhance the in vitro blebbing, by the disruption of genes involved in processes including the synthesis of proteins linking the outer membrane and the underlying peptidoglycan layer, envelope structure, and cellular stress [31,32,33] These blebs resulting from the hyperblebbing of genetically modified microorganisms have been called GMMA (Generalized Modules for Membrane Antigens). The affinity of the specific interaction between each TLR and its ligand starts from nanomolar concentrations of PAMPs, as in the case of TLR2, 3, 5, and 9 [60,65,66], or from higher ligand concentration, as for TLR4 [64], and it is different in different cells

PAMPs on OMVs

OMVs Compared to Classical Vaccines

Discussion