Efficacy of a novel virulence gene-deleted Salmonella Typhimurium vaccine for protection against Salmonella infections in growing piglets
ABSTRACT We have previously developed a novel attenuated Salmonella Typhimurium (S. Typhimurium) ΔcpxR Δlon vaccine. This study was carried out to examine whether this vaccine could effectively protect growing piglets against Salmonella infection. Attenuated S. Typhimurium secreting the B subunit of Escherichia coli heat-labile enterotoxin was also used as a mucosal adjuvant. Pregnant sows in groups A and B were primed and boosted with the vaccine and mucosal adjuvant, whereas sows in groups C, D and E received PBS. Piglets in groups A and C were intramuscularly primed with formalin-inactivated vaccine and orally boosted with live vaccine, while piglets in groups B, D and E received PBS. Piglets in groups A, B, C, and D were challenged with a wild type virulent S. Typhimurium at the 11th weeks of age. Colostrum sIgA and IgG titers in vaccinated groups A and B sows were approximately 50 and 40 times higher than those of non-vaccinated groups C, D and E sows (P<0.001). Serum IgG titers of group A piglets were also significantly higher than those of groups D and E piglets during the study (P<0.001). Furthermore, no clinical signs were observed in group A piglets during the entire experimental period after the challenge, while diarrhea was observed in many of the piglets in groups B, C, and D. No Salmonella was isolated from fecal samples of the groups A and C piglets on day 14 after challenge, whereas the challenge strain was isolated from several piglets in groups B and D. These results indicate that vaccination of the piglets with the vaccine and mucosal adjuvant in addition to vaccination of their sows induced effective protection against Salmonella infections in the growing piglets.
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- "The disease is usually characterized by self-limiting gastroenteritis in humans, but may occasionally cause fever and systemic infection  . Salmonellosis along with being a public health concern, is a economic problem as it also affects livestock breeding  . 26.9% of the human cases in the EU are caused by contaminated pork meat    . "
ABSTRACT: A major cause of salmonellosis in humans is the contamination of pork products. Infection in pigs can be controlled using bio-security programs, but they are not sufficient in countries where a high level of infection is recorded. In this context, the use of vaccines can represent a valid supplementary method of control. Recently, we have demonstrated that an attenuated strain of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium ΔznuABC) is protective against systemic and enteric salmonellosis in mouse and pig infection models, candidating this strain as an oral attenuated vaccine. In this study, we compared the efficacy of this attenuated Salmonella Typhimurium strain when administered orally or parenterally. Furthermore, in order to reproduce a pseudo-natural infection model, vaccinated pigs were allocated in the same pen with animals shedding virulent Salmonella Typhimurium. Animals were monitored weekly after vaccination and contact with infected piglets. Diarrhea and ataxia were recorded and Salmonella shedding was tested individually through bacterial culture. After four weeks of cohousing, piglets were euthanized, after which lymph nodes reactivity and gross lesions of the gut sections were scored at necropsy. Organs were submitted to microbiological and histological analyses. The data reported herein show that parenterally vaccinated animals do not shed the attenuated strain, and at the same time the absence of symptoms and decrease in virulent strain shedding in feces from day 6 after challenge demonstrated protection against infection induced by virulent Salmonella Typhimurium. In conclusion, our findings suggest that this is an alternative route of Salmonella Typhimurium ΔznuABC administration, without ignoring the advantages associated with oral vaccination.Vaccine 06/2014; 32(32). DOI:10.1016/j.vaccine.2014.05.066 · 3.49 Impact Factor
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- "Heterologous antigens fused with the LTB gene in attenuated Salmonella spp. have been used to induce humoral and cellular immune responses (Qiao et al., 2009; da Hora et al., 2011; Hur et al., 2011). The oral administration of LTB has been shown to promote heterologous protein exposure to the immune system by binding with galactosyl-N-acetylgala-ctosamylsialyl-galactosylglucosylceramide (GM1) ganglioside anchored on the surface of intestinal epithelial cells, thereby producing high titres of serum antibodies in mice (Liu et al., 2011). "
ABSTRACT: To investigate effective new rabies vaccines, a fusion protein consisting of the rabies virus (RV) glycoprotein and the heat-labile enterotoxin B subunit of Escherichia coli (LTB) was successfully constructed and delivered in a live attenuated Salmonella strain LH430. Mice were immunised with LH430 carrying pVAX1-G, pVAX1-G-LTB or pVAX1-ori-G-LTB. The antibody titres of mice immunised with oral LH430 carrying pVAX1-G-LTB or pVAX1-ori-G-LTB were significantly higher than those of pVAX1-G-immunised mice. The results of the challenge with the rabies virus standard strain (CVS-11) showed that the LH430 strain carrying the G-LTB gene induced immunity and elevated IL-2 levels in immunised mice ((∗∗)P<0.01), whereas LH430 carrying pVAX1-G did not contribute to protection. These results show that LH430 carrying recombinant G-LTB could provide overall immunity against challenge with CVS-11 and should be considered to be a potential rabies vaccine.Research in Veterinary Science 10/2011; 93(2):675-81. DOI:10.1016/j.rvsc.2011.09.015 · 1.51 Impact Factor
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ABSTRACT: To construct a novel live oral vaccine candidate for the prevention of pathogenic Escherichia coli infections in neonatal piglets, an expression and secretion plasmid and an attenuated Salmonella delivery system were used. The individual E. coli genes K88ac, K99, FasA, F41 and intimin adhesins were inserted into pBP244 containing asd, lepB, secA and secB, and these plasmids were transformed into a Salmonella Typhimurium ΔcpxR Δlon Δasd. Forty female BALB/c mice were divided into four groups, A to D (ten mice per group). Groups A and B were administered with the mixture containing all constructs and the S. Typhimurium containing pBP244 only as a control, respectively. Groups C and D were primed and boosted with the mixture and the S. Typhimurium harboring pBP244 only, respectively. Each recombinant adhesin secreted from the individual candidates was confirmed by Western blot analysis. The serum IgG and secretory IgA (sIgA) titers to individual adhesins in all immunized groups were higher than those in control. Furthermore, IgG and sIgA levels in group C were higher than those in group A, and the IgG1 titers were increased in Group C but IgG2a titers were similar or decreased in Group C compared to Group A. In addition, the vaccine strains were not detected in fecal samples of any immunized mice. The novel vaccine candidates are not only highly immunogenic, but also safe for vaccinated mice and environment. In addition, the immune responses can be more efficiently induced through the booster-administration.Journal of Veterinary Medical Science 05/2011; 73(10):1265-73. DOI:10.1292/jvms.11-0087 · 0.88 Impact Factor