Immunization of Pigs To Prevent Disease in Humans: Construction and Protective Efficacy of a Salmonella enterica Serovar Typhimurium Live Negative-Marker Vaccine

Abstract

Zoonotic infections caused by Salmonella enterica serovar Typhimurium pose a constant threat to consumer health, with the pig being a particularly major source of multidrug-resistant isolates. Vaccination, as a promising approach to reduce colonization and shedding, has been scarcely used, as it interferes with current control programs relying on serology as a means of herd classification. In order to overcome this problem, we set out to develop a negative-marker vaccine allowing the differentiation of infected from vaccinated animals (DIVA). Applying an immunoproteomic approach with two-dimensional gel electrophoresis, Western blot, and quadrupole time-of-flight tandem mass spectrometry, we identified the OmpD protein as a suitable negative marker. Using allelic exchange, we generated an isogenic mutant of the licensed live vaccine strain Salmoporc and showed that virulence of Salmoporc and that of the mutant strain, Salmoporc⌬ompD, were indistinguishable in BALB/c mice. In a pig infection experiment including two oral immunizations with Salmoporc⌬ompD and challenge with a multiresistant S. enterica serovar Typhimurium DT104 clinical isolate, we confirmed the protective efficacy of Salmoporc⌬ompD in pigs, showing a significant reduction of both clinical symptoms and colonization of lymph nodes and intestinal tract. OmpD immunogenic epitopes were determined by peptide spot array analyses. Upon testing of several 9-mer peptides, each including an immunogenic epitope, one peptide (positions F 100 to Y 108 ) that facilitated the detection of infected animals independent of their vaccination status (DIVA function) was identified. The approach described overcomes the problems currently limiting the use of bacterial live vaccines and holds considerable potential for future developments in the field.

Evaluation of three intervention strategies to reduce the transmission of Salmonella Typhimurium in pigs

“…Vaccination may thus hamper the use of serology for Salmonella monitoring programmes. Programmes that are based on bacteriology, new diagnostic tests that do not detect vaccine-induced antibodies (Selke et al, 2007), or new vaccines that are not detected by current ELISA methods (Leyman et al, 2011) are necessary if vaccination is to become a routine part of Salmonella control.…”

Use of an attenuated live Salmonella Typhimurium vaccine on three breeding pig units: A longitudinal observational field study

“…Trials have reported safety and some degree of efficacy when it has been used in experimental ST-challenge studies. These have involved vaccinating dams and/or pre-weaned piglets [18], or vaccinating weaners subsequently challenged by oral dosing [19,20] or by seeder pigs [21]. The rationale to vaccinate dams is to reduce shedding around farrowing and to provide passive immunity to offspring [22].…”

Parenteral administration of attenuated Salmonella Typhimurium ΔznuABC is protective against salmonellosis in piglets

“…Nontyphoidal salmonellosis (NTS) still has an important impact on public health in developed countries [3] and the consumption of pork is increasingly referred to as a major source of human infection [5,6]. Vaccination is one of the methods suggested to decrease the burden of S. Typhimurium at the swine farm level and to prevent dissemination of bacterial microorganisms through the pork production chain.…”

“…The disease is usually characterized by self-limiting gastroenteritis in humans, but may occasionally cause fever and systemic infection [1,2]. Salmonellosis along with being a public health concern, is a economic problem as it also affects livestock breeding [3,4]. 26.9% of the human cases in the EU are caused by contaminated pork meat [5][6][7][8].…”