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

Abstract

The initial virulence and invasiveness of a bacterial strain may play an important role in leading to a maximally efficacious attenuated live vaccine. Here we show that χ9909, derived from Salmonella Typhimurium UK-1 χ3761 (the most virulent S. Typhimurium strain known to us), is effective in protecting mice against lethal UK-1 and 14028S (less virulent S. Typhimurium strain) challenge. As opposed to this, 14028S-derived vaccine χ12359 induces suboptimal levels of protection, with survival percentages that are significantly lower when challenged with lethal UK-1 challenge doses. T-cell assays have revealed that significantly greater levels of Th1 cytokines IFN-γ and TNF-α were secreted by stimulated T-lymphocytes obtained from UK-1(ΔaroA) immunized mice than those from mice immunized with 14028S(ΔaroA). In addition, UK-1(ΔaroA) showed markedly higher colonizing ability in the spleen, liver, and cecum when compared to 14028S(ΔaroA). Enumeration of bacteria in fecal pellets has also revealed that UK-1(ΔaroA) can persist in the host for over 10 days whereas 14028S(ΔaroA) titers dropped significantly by day 10. Moreover, co-infection of parent strains UK-1 and 14028S resulted in considerably greater recovery of the former in multiple mucosal and gut associated lymphatic tissues. Mice immunized with UK-1(ΔaroA) were also able to clear UK-1 infection remarkably more efficiently from the target organs than 14028S(ΔaroA). Together, these results provide ample evidence to support the hypothesis that attenuated derivatives of parent strains with higher initial virulence make better vaccines.

Evaluation of a Salmonella Strain Isolated from Honeybee Gut as a Potential Live Oral Vaccine Against Lethal Infection of Salmonella Typhimurium

“…In Pakistan, prevalence studies on Salmonella have regularly pointed towards the higher prevalence of S. Typhi in human subjects (Ochiai et al 2008). In another prevalence study in Karachi, Pakistan, the prevalence percentage of S. Typhi from human subjects was reported to be 9.1% (Siddiqui et al 2015). The prevalence percentage of S. Typhi in the human subjects in this study was the highest among all the Salmonella strains.…”

“…For the detection of antibodies, the titer indirect hemagglutination test (IHAT) of Smith et al (1977) was used with minor modifications. The live Salmonella antigen (HB1) was used to sensitize RBC's using chromium chloride for antigen binding.…”

Antigen-encapsulating host extracellular vesicles derived from Salmonella-infected cells stimulate pathogen-specific Th1-type responses in vivo

“…The BMDMs have been obtained and cultured as previously described [ 6 ]. The overnight cultures of Salmonella enterica serovar Typhimurium, strain UK-1 χ3761 (wild-type), and χ9909 (Δ aroA vaccine strain) [ 58 ] were cultivated at 37°C in lysogeny broth (LB) media, shaking. Overnight bacterial cultures were diluted in new LB media in a 1:80 ratio to reach the optical density at 600 nm (OD 600 ) of 0.05 and grown until OD 600 was 0.50, followed by a wash in PBS before bacterial cultures were used for infections.…”

“…After 60 minutes of incubation, cells were treated with 1 μg/mL of LPS and incubated in DMEM without FBS or antibiotics for 24 hours. Exosomes were isolated from the cell culture media using the ultracentrifugation method as described [ 58 ].…”

Computational Identification of the Plausible Molecular Vaccine Candidates of Multidrug-Resistant Salmonella enterica

“…SsrB has been claimed as one of the most important factors for Salmonella's virulence by the fact that, a mutated ssrB, resulted in reduced ability of colonization on comparing with the wild type [70]. Moreover, one alteration in the gene ssrB, preferentially silencing the acquired DNA, can have a high contribution towards low transcription in the virulence factors of Salmonella [71].…”