Abstract
Twenty-eight adults received between 10(2) and 10(8)colony forming units of live Shigella dysenteriae type-1 vaccine SC599, attenuated by deletion of invasion (icsA), iron chelation (ent, fep) and shiga toxin A-subunit (stxA) genes, followed by ciprofloxacin on day 4. Dose-independent diarrhea or change in bowel habit was seen in 3 subjects, without dysentery, vaccinaemia or serious adverse events. Hematology and biochemical parameters were unchanged. Doses of 10(5) or greater induced dose-independent SD1 lipopolysaccharide-specific antibody secreting cell (ASC) responses. Geometric mean number of IgA ASCs per 10(6) PBMCs for 10(5), 10(6), 10(7) and 10(8) groups were respectively 41, 8.8, 26 and 8.5. Serum antibody responses were seen in three subjects. SC599 appears immunogenic with maximum tolerated dose greater than 10(8)CFU.
Publication types
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Clinical Trial, Phase I
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Adult
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Antibodies, Bacterial / blood
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Bacterial Proteins / genetics
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DNA-Binding Proteins / genetics
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Dysentery, Bacillary / prevention & control*
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Enterobactin / genetics
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Female
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Gene Deletion*
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Humans
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Male
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Protein Subunits / genetics
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Shiga Toxin / genetics
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Shigella Vaccines / administration & dosage
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Shigella Vaccines / adverse effects*
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Shigella Vaccines / immunology*
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Shigella dysenteriae / genetics
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Shigella dysenteriae / immunology*
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Transcription Factors / genetics
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Treatment Outcome
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Vaccines, Attenuated / administration & dosage
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Vaccines, Attenuated / adverse effects*
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Vaccines, Attenuated / agonists
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Vaccines, Attenuated / immunology*
Substances
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Antibodies, Bacterial
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Bacterial Proteins
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DNA-Binding Proteins
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Protein Subunits
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Shiga toxin subunit A
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Shigella Vaccines
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Transcription Factors
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Vaccines, Attenuated
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virG protein, Shigella flexneri
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Enterobactin
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Shiga Toxin