Abstract
PurposeNon-host-adapted Salmonella serovars, including the common human food-borne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), are opportunistic pathogens that can colonize food-producing animals without causing overt disease. Interventions against Salmonella are needed to enhance food safety, protect animal health and allow the differentiation of infected from vaccinated animals (DIVA).MethodologyAn attenuated S. Typhimurium DIVA vaccine (BBS 866) was characterized for the protection of pigs following challenge with virulent S. Typhimurium. The porcine transcriptional response to BBS 866 vaccination was evaluated. RNA-Seq analysis was used to compare gene expression between BBS 866 and its parent; phenotypic assays were performed to confirm transcriptional differences observed between the strains.ResultsVaccination significantly reduced fever and interferon-gamma (IFNγ) levels in swine challenged with virulent S. Typhimurium compared to mock-vaccinated pigs. Salmonella faecal shedding and gastrointestinal tissue colonization were significantly lower in vaccinated swine. RNA-Seq analysis comparing BBS 866 to its parental S. Typhimurium strain demonstrated reduced expression of the genes involved in cellular invasion and bacterial motility; decreased invasion of porcine-derived IPEC-J2 cells and swimming motility for the vaccine strain was consistent with the RNA-Seq analysis. Numerous membrane proteins were differentially expressed, which was an anticipated gene expression pattern due to the targeted deletion of several regulatory genes in the vaccine strain. RNA-Seq analysis indicated that genes involved in the porcine immune and inflammatory response were differentially regulated at 2 days post-vaccination compared to pre-vaccination.ConclusionEvaluation of the S. Typhimurium DIVA vaccine indicates that vaccination will provide both swine health and food safety benefits.
Highlights
In many countries, Salmonella is endemic and often asymptomatic in swine production, thereby complicating the control of this opportunistic animal health and human food-borne pathogen in pigs [1]
Salmonella faecal shedding and gastrointestinal tissue colonization were significantly lower in vaccinated swine
Typhimurium strain demonstrated reduced expression of the genes involved in cellular invasion and bacterial motility; decreased invasion of porcinederived IPEC-J2 cells and swimming motility for the vaccine strain was consistent with the RNA-Seq analysis
Summary
Salmonella is endemic and often asymptomatic in swine production, thereby complicating the control of this opportunistic animal health and human food-borne pathogen in pigs [1]. A review of our sowscreening data from a small number of farms in the USA with high health status (including specific-pathogen-free farms) found that 95 % of sows had serum antibodies to Salmonella LPS and ~20 % were actively shedding the pathogen in their faeces prior to farrowing [3]. These data indicate that, during their lifetime, most sows are exposed to Salmonella and piglets from a subset of these sows will most likely be exposed to Salmonella within days of farrowing. Two major hurdles for vaccines against Salmonella are avoiding interference with serological monitoring programs and demonstrating cross-protection against diverse Salmonella serovars with variable immunodominant
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