Salmonella typhi and S. typhimurium derivatives harbouring deletions in aromatic biosynthesis and Salmonella Pathogenicity Island-2 (SPI-2) genes as vaccines and vectors

Khan, Shahid A.; Stratford, Richard; Wu, Tao; McKelvie, Nicola D.; Bellaby, Trevor; Hindle, Zoë; Sinha, Katharine A.; Eltze, Shayne; Mastroeni, Pietro; Pickard, Derek; Dougan, Gordon; Chatfield, Steven N.; Brennan, Frank R.

doi:10.1016/s0264-410x(02)00410-3

Cited by 53 publications

(44 citation statements)

References 42 publications

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“…Of these attenuated vaccine strains, SC4A9 followed by SC2D2 and SC10B1 mutants were found to provide safe and protective efficacy in preventing the disease. Recently, serovar Typhi and serovar Typhimurium harboring defined deletions at ssaV and aroC have been demonstrated to serve as promising candidates both as human typhoid vaccines and as vaccine vectors for the delivery of heterologous antigens (31,39). We also found that the ssaV mutant of S. enterica serovar Choleraesuis prevented the clinical disease in pigs.…”

Section: Vol 73 2005 S Enterica Serovar Choleraesuis As Vaccine Camentioning

confidence: 73%

Novel AttenuatedSalmonella entericaSerovar Choleraesuis Strains as Live Vaccine Candidates Generated by Signature-Tagged Mutagenesis

McDonough

Palaniappan

et al. 2005

Infect Immun

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Section: Vol 73 2005 S Enterica Serovar Choleraesuis As Vaccine Camentioning

confidence: 73%

Novel AttenuatedSalmonella entericaSerovar Choleraesuis Strains as Live Vaccine Candidates Generated by Signature-Tagged Mutagenesis

McDonough

Palaniappan

et al. 2005

Infect Immun

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“…Many live attenuated Salmonella vaccines have been described and are generally more efficacious than killed vaccines (21,22). SPI1 and SPI2 mutants were identified as having vaccine potential in Salmonella enterica serovar Enteritidis (S. Enteritidis), Salmonella enterica serovar Typhimurium (S. Typhimurium), and Salmonella enterica serovar Typhi (S. Typhi) (23,24). In this study, we evaluated the efficacy of a candidate live-attenuated oral vaccine, S06004⌬SPI2, for PD and FT based on the virulence, changes in body weight and clinical symptoms, colonization, serum IgG response, peripheral lymphocyte proliferation response, and protective efficiency in susceptible HY-Line white chickens.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Salmonella enterica Serovar Pullorum Pathogenicity Island 2 Mutant as a Candidate Live Attenuated Oral Vaccine

Yin

Zhao

Wang

et al. 2015

Clin. Vaccine Immunol.

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Salmonella enterica serovar Pullorum (S. Pullorum) is a highly adapted pathogen that causes pullorum disease (PD), an important systemic disease of poultry that causes severe economic losses in developing countries. In the interests of developing a safe and immunogenic oral vaccine, the efficacy of a Salmonella pathogenicity island 2 (SPI2)-deleted mutant of S. Pullorum (S06004⌬SPI2) was evaluated in chickens. S06004⌬SPI2 was severely less virulent than the parental wild-type strain S06004 as determined by the 50% lethal dose (LD 50 ) for 3-day-old chickens when injected intramuscularly. Two-day-old chickens immunized with a single oral dose of S06004⌬SPI2 showed no differences in body weight or clinical symptoms compared with those in the negative-control group. S06004⌬SPI2 bacteria were not isolated from livers or spleens of immunized chickens after a short period of time, and specific humoral and cellular immune responses were significantly induced. Immunized chickens were challenged with S. Pullorum strain S06004 and Salmonella enterica serovar Gallinarum (S. Gallinarum) strain SG9 at 10 days postimmunization (dpi), and efficient protection against the challenges was observed. None of the immunized chickens died, the clinical symptoms were slight and temporary following challenge in immunized chickens compared with those in the control group, and these chickens recovered by 3 to 5 dpi. Overall, these results demonstrate that S06004⌬SPI2 can be used as a live attenuated oral vaccine. Salmonella enterica serovar Pullorum (S. Pullorum) is a highly adapted pathogen that causes pullorum disease (PD) in poultry. PD is an acute systemic disease with high morbidity and mortality in young chicks, and causes weight loss, decreased fertility and hatchability, lesions (peritonitis, perihepatitis, and so on), diarrhea, and reproductive tract abnormalities in infected adults. In addition, S. Pullorum can be transmitted to chicks through eggs (1, 2). PD is rare in most developed countries because of modern poultry-rearing facilities and well-established disease control programs, but in recent years, its incidence has been frequently reported in developing countries (3). Salmonella enterica serovar Gallinarum (S. Gallinarum) causes the severe systemic disease fowl typhoid (FT) in young and adult chickens, and multilocus enzyme electrophoresis and comparative sequence analyses show it is closely related to S. Pullorum (4-6). Although largely eradicated in several countries, FT still causes significant morbidity and mortality worldwide, which results in substantial economic losses (7).Several strategies have been used to prevent and control these diseases, such as antimicrobial therapy, biosecurity practices, and effective vaccination programs. Antimicrobial therapy can result in multidrug-resistant bacteria in poultry. In addition, these multidrug-resistant pathogens can be transmitted to humans via the food chain (8, 9). Vaccination is one of the most effective methods of preventing Salmonella infections (10). Killed vaccin...

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“…purA and purE) [57,58], in the production of adenylate cyclase (cya) or the cyclic AMP receptor protein (crp) [59], or with mutations affecting the global regulatory system (phoP/phoQ) [60] or the gene encoding Cdt (colonization of deep tissues) [61] have been investigated in mice as potential live vaccine candidates. Strains of S. Typhimurium with mutations in the Salmonella pathogenicity island-2 (SPI-2) are also attenuated in mice [62][63][64][65]. Further, the phoP/phoQ and the ΔaroC ΔssaV S. Typhimurium mutant strains have been reported to be safe and elicit specific antibodies and IgA antibody-secreting cell responses to the heterologous antigens as well as to the carriers LPS [56,66,67] in human volunteers.…”

Section: Discussionmentioning

confidence: 99%

Immunological responses against Salmonella enterica serovar Typhimurium Braun lipoprotein and lipid A mutant strains in Swiss-Webster mice: Potential use as live-attenuated vaccines

König

Sha

et al. 2008

Microbial Pathogenesis

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We generated and characterized Salmonella enterica serovar Typhimurium mutants that were deleted for the genes encoding Braun lipoprotein (lpp) alone or in conjunction with the msbB gene, which codes for an enzyme required for the acylation of the lipid A moiety of lipopolysaccharide. Two copies of the lpp gene, designated as lppA and lppB, exist on the chromosome of S. Typhimurium. These mutants were highly attenuated in a mouse infection model and induced minimal histopathological changes in mouse organs compared to those seen in infection with wild-type (WT) S. Typhimurium. The lppB/msbB and the lppAB/msbB mutants were maximally attenuated, and hence further examined in this study for their ability to induce humoral and cellular immune responses. Importantly, infection of out-bred Swiss-Webster mice with the mutant S. Typhimurium generated superior T helper cell type 2 (Th2) responses compared to WT S. Typhimurium, as determined by measuring IgG subclasses and cytokines. WT S. Typhimurium induced higher levels of IgG2a in sera of infected mice, while the lppB/msbB and lppAB/msbB mutants mounted higher levels of IgG1 as determined by an enzyme-linked immunosorbent assay. Mice immunized with lppB/msbB and lppAB/msbB mutants rapidly cleared WT S. Typhimurium upon subsequent rechallenge, and naïve mice passively immunized with sera from animals infected with S. Typhimurium mutants were protected against subsequent challenge with WT S. Typhimurium. Splenic T cells produced higher levels of interferon-gamma following ex vivo exposure to WT S. Typhimurium, while splenic T cells infected with the above-mentioned two mutants evoked higher levels of interleukin-6. Further, mice infected with lppB/msbB and lppAB/msbB mutants showed much higher levels of splenic T cell activation as measured by CD44 + expression on CD4 + T cells by flow cytometry and by incorporation of 3 H-thymidine compared to mice that were infected with WT S. Typhimurium. We expect the lppB/msbB and lppAB/msbB mutants to be excellent live-attenuated vaccine candidates, because they induced minimal inflammatory responses and evoked stronger and specific antibody and cellular immune responses.

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Salmonella typhi and S. typhimurium derivatives harbouring deletions in aromatic biosynthesis and Salmonella Pathogenicity Island-2 (SPI-2) genes as vaccines and vectors

Cited by 53 publications

References 42 publications

Novel AttenuatedSalmonella entericaSerovar Choleraesuis Strains as Live Vaccine Candidates Generated by Signature-Tagged Mutagenesis

Novel AttenuatedSalmonella entericaSerovar Choleraesuis Strains as Live Vaccine Candidates Generated by Signature-Tagged Mutagenesis

Evaluation of the Salmonella enterica Serovar Pullorum Pathogenicity Island 2 Mutant as a Candidate Live Attenuated Oral Vaccine

Immunological responses against Salmonella enterica serovar Typhimurium Braun lipoprotein and lipid A mutant strains in Swiss-Webster mice: Potential use as live-attenuated vaccines

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