Safety and Immunogenicity of Two Salmonella typhi Vi Capsular Polysaccharide Vaccines

Tacket, Carol O.; Ferreccio, Catterine; Robbins, John B.; Tsai, Chau-Ming; Schulz, Dominique; Cadoz, M; Goudeau, Alain; Levine, Myron M.

doi:10.1093/infdis/154.2.342

Cited by 102 publications

(40 citation statements)

References 11 publications

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“…An inhibition of complement-mediated phagocytosis is a virulence property conferred by the capsular polysaccharides of other invasive bacterial pathogens, including K. pneumoniae, N. meningitidis, S. aureus, S. pneumoniae, and E. coli isolates associated with extraintestinal infections (2,7,10,15,35). Vaccination with purified Vi capsular polysaccharide confers protection against typhoid fever, suggesting that dissemination of S. Typhi involves an extracellular phase that renders the pathogen susceptible to Fc receptor-mediated phagocytosis and/or serum-mediated killing (19,29,32). The nature of this extracellular phase remains poorly characterized.…”

Section: Discussionmentioning

confidence: 99%

The Vi Capsular Polysaccharide Prevents Complement Receptor 3-Mediated Clearance of Salmonella enterica Serotype Typhi

et al. 2011

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Salmonella enterica serotype Typhi (S. Typhi) causes an estimated 21 million annual cases of typhoid fever, a severe systemic infection resulting in 200,000 to 600,000 fatalities per year (5, 37). After ingestion, S. Typhi invades the intestinal mucosa, but symptoms develop only after an average incubation period of 2 weeks (23). The relatively long incubation period of typhoid fever suggests that S. Typhi can evade or suppress detection by the innate immune system during the initial stages of infection (26,28,33). However, the virulence mechanisms that enable S. Typhi to evade components of the innate immune system early after infection have long remained elusive.One arm of the innate immune system involved in detection of invasive microbes is the complement system (9, 38). Complement deposition on the bacterial cell surface and opsonophagocytosis can be prevented by capsular polysaccharides of invasive Gramnegative pathogens, including Neisseria meningitidis, Klebsiella pneumoniae, and Escherichia coli isolates associated with extraintestinal infections (1,15,16,35). S. Typhi produces the virulence (Vi) capsular polysaccharide (8), which is encoded by the viaB locus (17). The viaB locus is a 14-kb DNA region containing genes required for the regulation (tviA), the biosynthesis (tviBCDE), and the export (vexABCDE) of the Vi capsular polysaccharide (36). In S. Typhi, the role of the Vi capsular polysaccharide in reducing complement deposition has not been convincingly demonstrated. The viaB locus of S. Typhi is located on a 134-kb DNA region, termed Salmonella pathogenicity island 7 (SPI-7) (24). SPI-7 is genetically unstable and can be lost upon laboratory passage (3,22). Clinical S. Typhi isolates expressing the Vi capsular polysaccharide tend to bind less complement on their surface in vitro than clinical isolates lacking capsule expression (20). While this report concludes that the Vi capsular polysaccharide inhibits opsonophagocytosis, the evidence is not conclusive, because it is based on comparison of nonisogenic, clinical S. Typhi isolates. Genetic differences between these clinical isolates were not defined but likely included the entire SPI-7 region. Additionally, the in vivo relevance of phenotypes attributed to the Vi capsular polysaccharide remains to be established using animal models.With the exception of higher primates, vertebrate hosts are resistant to infection with the human-adapted S. Typhi, which has prevented the use of animal models to investigate the in vivo relevance of results obtained using tissue culture. While mice orally inoculated with S. Typhi are not suited to study the development of typhoid fever, we reasoned that this animal model could be used for studying isolated steps during infection, provided that the relevant interactions were not species specific. Here we investigated the role of the Vi capsular polysaccharide on complement-mediated phagocytosis and its impact on bacterial clearance during an infection. MATERIALS AND METHODSBacterial strains and culture conditions. Vi...

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Section: Discussionmentioning

confidence: 99%

The Vi Capsular Polysaccharide Prevents Complement Receptor 3-Mediated Clearance of Salmonella enterica Serotype Typhi

et al. 2011

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“…NTS thus represents a major public health concern, especially with the increasing number of antibiotic-resistant isolates being reported (9,10). There are currently three vaccines licensed for use in humans, all targeting typhoidal Salmonella: the live attenuated oral vaccine S. Typhi Ty21a, Vi capsule polysaccharide vaccine, and Vi polysaccharide conjugated with tetanus toxoid (11)(12)(13)(14). Despite extensive efforts, no human vaccine targeting NTS has yet been licensed.…”

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Salmonella Serogroup C: Current Status of Vaccines and Why They Are Needed

Fuche

Sow

Simon

et al. 2016

Clin Vaccine Immunol

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“…Immunization with purified Vi polysaccharide was shown to protect mice against intraperitoneal challenge with virulent serovar Typhi administered with gastric mucin (29,46,62). More important, in controlled human field trials, parenteral immunization with nondenatured purified Vi polysaccharide, which elicits serum immunoglobulin G (IgG) Vi antibody (25,49), has conferred a moderate level of protection against typhoid fever (1,25,26). Due to clinical data demonstrating safety, immunogenicity, and efficacy, purified Vi polysaccharide is currently a licensed parenteral typhoid vaccine.…”

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confidence: 99%

Constitutive Expression of the Vi Polysaccharide Capsular Antigen in AttenuatedSalmonella entericaSerovar Typhi Oral Vaccine Strain CVD 909

et al. 2000

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Safety and Immunogenicity of Two Salmonella typhi Vi Capsular Polysaccharide Vaccines

Cited by 102 publications

References 11 publications

The Vi Capsular Polysaccharide Prevents Complement Receptor 3-Mediated Clearance of Salmonella enterica Serotype Typhi

The Vi Capsular Polysaccharide Prevents Complement Receptor 3-Mediated Clearance of Salmonella enterica Serotype Typhi

Salmonella Serogroup C: Current Status of Vaccines and Why They Are Needed

Constitutive Expression of the Vi Polysaccharide Capsular Antigen in AttenuatedSalmonella entericaSerovar Typhi Oral Vaccine Strain CVD 909

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