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Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate
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Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate
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Journal Article
Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate
2008
Overview
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 ingested escalating doses of WRSd1 ranging from 10
3 to 10
7
CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuated
Shigella vaccine must colonize well.
Publisher
Elsevier Ltd,Elsevier
Subject
/ Adult
/ Antibodies, Bacterial - analysis
/ Bacterial Proteins - genetics
/ Biological and medical sciences
/ DNA-Binding Proteins - genetics
/ Female
/ Fundamental and applied biological sciences. Psychology
/ Humans
/ Male
/ Shigella
/ Shigella dysenteriae - immunology
/ Shigella Vaccines - adverse effects
/ Shigella Vaccines - immunology
/ Transcription Factors - genetics
/ Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
