Evaluation in volunteers of a candidate live oral attenuated Salmonella typhi vector vaccine.

Hone, David M.; Tacket, Carol O.; Harris, Andrea M.; B, Kay; Losonsky, G; Levine, Myron M.

doi:10.1172/jci115876

Cited by 83 publications

(53 citation statements)

References 45 publications

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“…There was no evidence for systemic spread of ZH9, since bacteria were not detected in the blood at any time. Serovar Typhi Ty2 aro derivatives reproducibly cause bacteremia at the doses utilized in this study (21,44,45) and, although a serovar Typhi ⌬aro strain was not utilized in this study, since it was ethically inappropriate, we feel these preliminary data are sufficient to suggest that the ssaV mutation was modulating the virulence of this strain, thus reducing the bloodstream survival of ZH9 and eliminating postimmunization bacteremia, which has been identified as a key safety feature in potential live oral typhoid vaccines. This would be in keeping with data from animal models demonstrating that a functional SPI-2 system is required for intracellular survival and establishment of the early bloodstream phase of serovar Typhi infection.…”

Section: Discussionmentioning

confidence: 93%

“…Mutant derivatives of Ty2 have been found to be less virulent than derivatives of other wild-type serovar Typhi strains containing identical mutations (21,45), and although not demonstrated conclusively, this has been attributed to the presence of an rpoS mutation in the Ty2 parent strain (6,37). The safety and immunogenicity of the Salmonella strains used here was established in preclinical murine studies with serovar Typhimurium.…”

Section: Discussionmentioning

confidence: 98%

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Characterization of Salmonella enterica Derivatives Harboring Defined aroC and Salmonella Pathogenicity Island 2 Type III Secretion System ( ssaV ) Mutations by Immunization of Healthy Volunteers

Hindle

Chatfield

Phillimore³

et al. 2002

Infect Immun

194

145

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The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica serovar Typhi (Ty2 ⌬aroC ⌬ssaV, designated ZH9) and S. enterica serovar Typhimurium (TML ⌬aroC ⌬ssaV, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 10 7 , 10 8 , or 10 9 CFU. ZH9 was well tolerated, not detected in blood, nor persistently excreted in stool. Six of nine volunteers elicited anti-serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting cell (ASC) responses, with three of three vaccinees receiving 10 8 and two of three receiving 10 9 CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 10 8 and 10 9 CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 10 9 CFU of WT05 mounted detectable serovar Typhimurium LPS-specific ASC responses and serum antibody responses were variable. These data indicate that mutations in type III secretion systems may provide a route to the development of live vaccines in humans and highlight significant differences in the potential use of serovars Typhimurium and Typhi.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Characterization of Salmonella enterica Derivatives Harboring Defined aroC and Salmonella Pathogenicity Island 2 Type III Secretion System ( ssaV ) Mutations by Immunization of Healthy Volunteers

Hindle

Chatfield

Phillimore³

et al. 2002

Infect Immun

194

145

View full text Add to dashboard Cite

show abstract

“…In concordance, S. Typhi CVD906, a live vaccine, derived from ISP1820 with deletion mutations caused fever and other adverse reactions in humans in aroC and aroD [73], is highly immunogenic but [72,74]. This is in contrast to the S. Typhi CVD908 Ty2 ΔaroC ΔaroD vaccine strain, which did not cause any adverse effects [72].…”

Section: Vaccine Developmentmentioning

confidence: 99%

Regulation of Vi Capsular Polysaccharide Synthesis in Salmonella enterica Serotype Typhi

Santander

Roland

Curtiss

2008

J Infect Dev Ctries

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The synthesis of Vi polysaccharide, a major virulence determinant in Salmonella enterica serotype Typhi (S. Typhi), is under the control of two regulatory systems, ompR-envZ and rscB-rscC, which respond to changes in osmolarity. Some S. Typhi isolates exhibit over-expression of Vi polysaccharide, which masks clinical detection of LPS O-antigen. This variation in Vi polysaccharide and O-antigen display (VW variation) has been observed since the initial studies of S. Typhi. We have reported that the status of the rpoS gene is responsible for this phenomenon. We review the regulatory network of the Vi polysaccharide, linking osmolarity and RpoS expression. Also, we discuss how this may impact live attenuated Salmonella vaccine development.

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“…Indeed, new vaccines have been developed. Further, it has been found that a highly immunogenic live oral Salmonella vaccine would ideally be suited as a carrier of genes that express protective antigens cloned from other antigens (3)(4)(5) and such hybrid recombinant Salmonella vaccines are expected to invoke protective immunity against both the carrier strains as well as the foreign antigens (6). This is the basis of Salmonella vaccine vector and this review seeks to illustrate this milestone in the scientific research done to date.…”

Section: Introductionmentioning

confidence: 99%

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

2008

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Salmonella (S.) typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector. Cellular & Molecular Immunology. 2008;5(2):91-97.

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Evaluation in volunteers of a candidate live oral attenuated Salmonella typhi vector vaccine.

Abstract: Clin. Invest. 1992. 90:412-420.)

Cited by 83 publications

References 45 publications

Characterization of Salmonella enterica Derivatives Harboring Defined aroC and Salmonella Pathogenicity Island 2 Type III Secretion System ( ssaV ) Mutations by Immunization of Healthy Volunteers

Characterization of Salmonella enterica Derivatives Harboring Defined aroC and Salmonella Pathogenicity Island 2 Type III Secretion System ( ssaV ) Mutations by Immunization of Healthy Volunteers

Regulation of Vi Capsular Polysaccharide Synthesis in Salmonella enterica Serotype Typhi

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

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