Bacterial ghosts as adjuvants: mechanisms and potential

Abstract

Bacterial ghosts (BG) are empty cell envelopes derived from Gram-negative bacteria. They contain many innate immunostimulatory agonists, and are potent activators of a broad range of cell types involved in innate and adaptive immunity. Several considerable studies have demonstrated the effectiveness of BG as adjuvants as well as their ability to induce proinflammatory cytokine production by a range of immune and non-immune cell types. These proinflammatory cytokines trigger a generalized recruitment of T and B lymphocytes to lymph nodes that maximize the chances of encounter with their cognate antigen, and subsequent elicitation of potent immune responses. The plasticity of BG has allowed for the generation of envelope-bound foreign antigens in immunologically active forms that have proven to be effective vaccines in animal models. Besides their adjuvant property, BG also effectively deliver DNA-encoded antigens to dendritic cells, thereby leading to high transfection efficiencies, which subsequently result in higher gene expressions and improved immunogenicity of DNA-based vaccines. In this review, we summarize our understanding of BG interactions with the host immune system, their exploitation as an adjuvant and a delivery system, and address important areas of future research interest.

Optically responsive delivery platforms: from the design considerations to biomedical applications

“…They can be produced by controlled expression of the cloned lysis gene E from bacteriophage species, generating a lysis tunnel structure within the envelope of the living bacteria [249]. Bacterial ghosts keep cellular morphology similar to native bacteria, where the entire surface structures including adhesins, membrane proteins, lipopolysaccharides, and the peptidoglycan layer are preserved [250]. Drug carriers can be also obtained from bacterial outer membrane vesicles [251].…”

Induction of Mucosal Humoral Immunity by Subcutaneous Injection of an Oil-emulsion Vaccine against <i>Salmonella enterica</i> subsp. <i>enterica</i> serovar Enteritidis in Chickens

“…Various types of Salmonella vaccines have been evaluated, including one that used bacterial ghosts as the antigen 6) . The tested vaccines have induced specific IgG and IgA, cellular immunity with increases in CD4 + and CD8 + T cells, and reduction of egg contamination 1) .…”

Anti-Idiotype Vaccine Provides Protective Immunity Against Vibrio Harveyi in Grouper (Epinephelus Coioides)

“…These enhanced activities elicited by anti-Id IgG (Fab) appear to be a consequence of their internal images showing more comprehensive epitopes of protein and non-protein antigens of V. harveyi. Generally, due to the harsh formalin inactivation process, some essential structural and immunogenic components of microorganisms are denatured to result in inefficient immune responses [15]. Formalin-inactivated V. harveyi bacteria used in this study, therefore, could not show more comprehensive epitopes than those displayed by anti-Id IgG (Fab) and thus caused low immunity (Figures 4 and 5) and protection ( Figure 6) against the highly virulent V. harveyi (Vh MML-1).…”

“…Vaccines based on inactivated (killed) bacteria are currently the most commonly used aquatic animal vaccines that can display diverse bacterial antigens [14]. However, the harsh activation processes, such as treatment of bacteria with formalin, heat, or ultraviolet light, induce the denaturation of bacterial immunogenic epitopes or conformations, thereby resulting in impaired function and non-efficient immune responses [15]. More effort is therefore needed to improve not only the immunogenic epitope integrity presented by vaccines, but also the immune responses and protection they induce in animals.…”