Phase 1 clinical trial of live attenuated Shigella dysenteriae type-1 DeltaicsA Deltaent Deltafep DeltastxA:HgR oral vaccine SC599 in healthy human adult volunteers.

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.
Authors	Christine Sadorge, Anna Ndiaye, Nathalie Beveridge, Schale Frazer, Rafaela Giemza, Nathalie Jolly, Julie Johnson, Helen Liddy, Catherine A Cosgrove, Paola Allavena, Alberto Mantovani, Stéphane Béchet, Annick Fontaine-Thompson, George E Griffin, Francis Dupont, Philippe J Sansonetti, David J M Lewis
Journal	Vaccine (Vaccine) Vol. 26 Issue 7 Pg. 978-87 (Feb 13 2008) ISSN: 0264-410X [Print] Netherlands
PMID	18207287 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibodies, Bacterial Bacterial Proteins DNA-Binding Proteins Protein Subunits Shiga toxin subunit A Shigella Vaccines Transcription Factors Vaccines, Attenuated virG protein, Shigella flexneri Enterobactin Shiga Toxin
Topics	Administration, Oral Adult Antibodies, Bacterial (blood) Bacterial Proteins (genetics) DNA-Binding Proteins (genetics) Dysentery, Bacillary (prevention & control) Enterobactin (genetics) Female Gene Deletion Humans Male Protein Subunits (genetics) Shiga Toxin (genetics) Shigella Vaccines (administration & dosage, adverse effects, immunology) Shigella dysenteriae (genetics, immunology) Transcription Factors (genetics) Treatment Outcome Vaccines, Attenuated (administration & dosage, adverse effects, agonists, immunology)

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