A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges

Abstract

Salmonella enteritidis and Salmonella typhimurium are important food-borne bacterial pathogens, which are responsible for diarrhea and gastroenteritis in humans and animals. In this study, S. typhimurium bacterial ghost (STG) was generated based on minimum inhibitory concentration (MIC) of sodium hydroxide (NaOH). Experimental studies performed using in vitro and in vivo experimental model systems to characterize effects of STG as a vaccine candidate. When compared with murine macrophages (RAW 264.7) exposed to PBS buffer (98.1%), the macrophages exposed to formalin-killed inactivated cells (FKC), live wild-type bacterial cells and NaOH-induced STG at 1 × 108 CFU/mL showed 85.6%, 66.5% and 84.6% cell viability, respectively. It suggests that STG significantly reduces the cytotoxic effect of wild-type bacterial cells. Furthermore, STG is an excellent inducer for mRNAs of pro-inflammatory cytokine (TNF-α, IL-1β) and factor (iNOS), anti-inflammatory cytokine (IL-10) and dual activities (IL-6) in the stimulated macrophage cells. In vivo, STG vaccine induced humoral and cellular immune responses and protection against homologous and heterologous challenges in rats. Furthermore, the immunogenicity and protective efficacy of STG vaccine were compared with those of FKC and non-vaccinated PBS control groups. The vaccinated rats from STG group exhibited higher levels of serum IgG antibody responses, serum bactericidal antibodies, and CD4+ and CD8+ T-cell populations than those of the FKC and PBS control groups. Most importantly, after challenge with homologous and heterologous strains, the bacterial loads in the STG group were markedly lower than the FKC and PBS control groups. In conclusion, these findings suggest that the STG vaccine induces protective immunity against homologous and heterologous challenges.

Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and 14028S: Importance of inherent virulence

“…A multitude of vaccine development endeavors utilizing attenuated live bacteria, whole-cell killed vaccines, and subunit vaccines aimed at inducing long-term, cross protective immunity against multiple Salmonella NTS serovars are underway [ 6 – 10 ]. The ability of live attenuated Salmonella strains to stimulate strong humoral and cellular immunity has rendered them as an attractive option for development as homologous vaccines and for use as carriers of heterologous antigens [ 11 – 14 ].…”

New technologies in developing recombinant‐attenuated bacteria for cancer therapy

“…After the tunnel structure forms, bacterial cytoplasm is released into the extracellular environment, leaving behind cell envelopes known as BGs (Witte & Lubitz, 1989; Witte et al, 1990). Since this process does not cause any denaturation to envelope structures, one of the main characteristics of BGs is the preservation of surface immunostimulatory elements, such as LPS, peptidoglycan, and flagella, showing a potential for BGs used as a candidate vaccine against respective pathogens (Hoseini Shahidi et al, 2019; Vinod et al, 2017). Moreover, BGs with the perfect adjuvant activity and a high loading capacity can serve as a carrier for delivery of heterologous antigens and DNA vaccines (Hajam et al, 2017).…”

Harnessing the Immunomodulatory Properties of Bacterial Ghosts to Boost the Anti-mycobacterial Protective Immunity

“…Integration of the 91 amino-acid polypeptide E in the bacterial envelope triggers a fusion process of the inner and outer membranes to form a transmembrane tunnel structure through which the cytoplasmic content is expelled driven by a proton-motive force (28, 29). To date, BG have been made from a variety of pathogens including Escherichia coli K12 (30), enterotoxigenic and enterohemaorrhagic E. coli (EHEC, ETEC) (31), Helicobacter pylori (32), Salmonella typhimurium (33), S. enteritidis (34), and Vibrio cholerae (35) for both veterinary and clinical vaccine purposes. BG have also been evaluated as drug delivery (36) and adjuvant (37) systems.…”