Abstract
Salmonella Typhimurium infection via foodborne transmission remains a major public health threat even in developed countries. Vaccines have been developed to reduce the disease burden at the pre-harvest stage, but the cell-mediated immune response against intracellular invasion of the pathogen is not sufficiently elicited by conventional killed Salmonella vaccines, which are safer than live vaccines. In this study, we developed a genetically inactivated vaccine candidate by introducing lysis plasmid pJHL454 harboring the λ phage holin–endolysin system into S. Typhimurium; we designated this vaccine JOL1950. In vitro expression of endolysin was validated by immunoblotting, and complete inactivation of JOL1950 cells was observed following 36 h of the lysis. Electron microscopic examinations by scanning electron microscopy and immunogold labeling transmission EM revealed conserved surface antigenic traits of the JOL1950 cells after lysis. An in vivo immunogenicity study in mice immunized with lysed cells showed significantly increased serum IgG, IgG1, and IgG2a levels. Further, we observed markedly increased in vitro cell proliferation and upregulation of Th1, Th2, and Th17 cytokines in the repulsed splenic T-cells of immunized mice. In dendritic cells (DCs) treated with lysed JOL1950, we observed a significant increase in dendritic cell activation, co-stimulatory molecule production, and levels of immunomodulatory cytokines. In addition, Th1 and Th17 cytokines were also released by naïve CD4+ T-cells pulsed with primed DCs. Lysed JOL1950 also protected against lethal challenge in immunized mice. Together, these results indicate that our vaccine candidate has great potential to induce cell-mediated immunity against S. Typhimurium by facilitating the activation of DCs.
Highlights
Nontyphoidal salmonellosis (NTS) attributable to foodborne transmission poses a substantial public health challenge worldwide [1]
Given that a conventional killed vaccine against salmonellosis failed to induce proper cell-mediated immunity (CMI) [19], which is required to defend against intracellular invasion and multiplication of the pathogen, we investigated the ability of our vaccine construct to be efficiently internalized by dendritic cells (DCs), which mediate T cell-related adaptive immunity [20]
No band was detected in lane 1 (Figure 1A), which contained proteins extracted from cells grown under conditions repressing the activation of the lysis cassette
Summary
Nontyphoidal salmonellosis (NTS) attributable to foodborne transmission poses a substantial public health challenge worldwide [1]. Given the importance of a “farm-to-fork” approach for the control of zoonotic food-borne diseases [8], development of effective vaccine candidates against salmonellosis responsible for human illnesses could address public health concerns about zoonotic infection through consumption of contaminated animal meats. Typhimurium have a potential as a live attenuated vaccine candidate against the infection [10, 11]. New and efficient vaccine candidates that are easy to administer and that confer high immunogenicity are required to help protect against food-borne salmonellosis at the pre-harvest level. It has been reported that bacteria cell lysis mediated by gene E is not complete [15, 16], which has raised concerns about the safety of BG vaccines. This work makes a vital contribution toward protecting against food-borne salmonellosis
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