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In order to establish a human challenge model of Shigella related disease for vaccine testing, a dose-escalating inpatient trial was performed. Three groups of 12 healthy adult volunteers were orally challenged with 93,440 and 1680CFU of Shigella sonnei strain 53G. Subjects were admitted to the Vaccine Trial Centre (VTC) at Mahidol University in Bangkok, Thailand. The primary purpose of this study...
Accurately assessing mucosal immune responses to candidate vaccines remains a technical challenge. ELISPOT is widely used as a surrogate of mucosal immune response by directly enumerating circulating antibody secreting cells (ASCs), while antibody in lymphocyte supernatant (ALS) titers the total amount of antibody secreted by ASC ex vivo using ELISA. ALS is more practical than ELISPOT because the...
Among Shigella serotypes Shigella dysenteriae type 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a live S. dysenteriae 1 strain attenuated by deletion of the virG(icsA) gene, which encodes a protein that mediates intercellular spread, and stxA and stxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects...
Recent clinical trials involving live attenuated Shigella vaccine strains SC602 and WRSS1 have revealed that deletion of the virG(icsA) gene dramatically reduces virulence in human volunteers. These strains can be given at low oral doses and induce a strong, and in some cases, protective immune responses. However, residual vaccine associated reactogenicity suggests that further attenuation is required...
Shigella and Salmonella kill host cells and trigger inflammatory responses by mechanisms that are not fully understood. The goal of this review is to reevaluate key observations reported over the past 15 years and, whenever possible, to provide a chronological perspective as to how our understanding of the pathways by which Shigella and Salmonella kill host cells has evolved.
Human challenge studies with EcSf2a-2, an aroD deletion-attenuated Escherichia coliK12 -Shigella flexneri hybrid vaccine expressing S. flexneri 2a somatic antigen and the invasive phenotype indicated that, at doses of 2 10 9 bacteria, EcSf2a-2 was immunogenic but also reactogenic and therefore not sufficiently attenuated. Two factors that may contribute to the residual reactogenicity are...
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