OMV Vaccines and the Role of TLR Agonists in Immune Response

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.

Effect of O-Antigen Chain Length Regulation on the Immunogenicity of Shigella and Salmonella Generalized Modules for Membrane Antigens (GMMA)

“…The multiplicity and geometry of antigen display can favor efficient BCR crosslinking, delivering strong activation signals to the B-cells independently from polysaccharide length [ 28 ]. Moreover, GMMA contain different TLR agonists, including lipid A and lipoproteins, able to provide synergistic TLR signaling to B-cells [ 5 ], as confirmed by MAT.…”

“…Recently, generalized modules for membrane antigens (GMMA) technology has been proposed as an alternative approach to traditional glycoconjugate vaccines for OAg delivery [ 3 ]. GMMA are outer membrane exosomes released from Gram-negative bacteria genetically engineered to increase blebbing (e.g., through deletion of the tolR gene) and reduce reactogenicity, usually by modifying the lipid A acylation pattern (e.g., through the deletion of the htrB and msbB genes) [ 4 , 5 ]. GMMA display the OAg in an outer membrane context and have been proven to be non-inferior compared to equivalent glycoconjugate vaccines in preclinical studies [ 6 , 7 ].…”

Outer Membrane Vesicles (OMVs) Produced by Gram-Negative Bacteria: Structure, Functions, Biogenesis, and Vaccine Application

“…OMVs are at the interface between traditional and new methods of vaccine production and represent a feasible opportunity to control various infectious diseases, such as nosocomial infections, enteric diseases, tuberculosis, meningitis, and whoop coughing that remain a health problem in children and young adults [36]. Vesicles presented advantages as a vaccine candidate because they are nonreplicative particles so cannot cause the disease, work as self-adjuvating, small size and particle shape facilitate the distribution throughout the body, highly stable at varying temperatures, elicit long-term memory responses, and induce both humoral and cellular mediated immune responses against OMV-presented antigens [56,125,[131][132][133][134][135].…”

Recent Advances in the Pursuit of an Effective Acinetobacter baumannii Vaccine

“…OMVs are composed of a wide variety of bacterial components, including DNA, RNA, lipo- and polysaccharides, and proteins. As such, OMVs are multivalent in nature and provide multiple antigens that can elicit both antibody and T cell responses against numerous bacterial targets [ 78 ]. Previous studies have already validated OMV-based vaccines using a diverse array of bacteria including Escherichia coli [ 79 , 80 , 81 ], Bordetella pertussis [ 82 , 83 ], Burkholderia pseudomallei [ 84 , 85 , 86 , 87 ], and even a commercially available vaccine for Neisseria meningitidis serogroup B [ 88 , 89 ].…”