title: 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.affiliation: Centre de Recherche Vaccinale et Biomédicale, Institut Pasteur, 75724 Paris Cedex 15, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Sadorge
authors.forename: Anna
authors.initials: A
authors.lastname: Ndiaye
authors.forename: Nathalie
authors.initials: N
authors.lastname: Beveridge
authors.forename: Schale
authors.initials: S
authors.lastname: Frazer
authors.forename: Rafaela
authors.initials: R
authors.lastname: Giemza
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jolly
authors.forename: Julie
authors.initials: J
authors.lastname: Johnson
authors.forename: Helen
authors.initials: H
authors.lastname: Liddy
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Cosgrove
authors.forename: Paola
authors.initials: P
authors.lastname: Allavena
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Stéphane
authors.initials: S
authors.lastname: Béchet
authors.forename: Annick
authors.initials: A
authors.lastname: Fontaine-Thompson
authors.forename: George E
authors.initials: GE
authors.lastname: Griffin
authors.forename: Francis
authors.initials: F
authors.lastname: Dupont
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.forename: David J M
authors.initials: DJ
authors.lastname: Lewis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004405:Dysentery, Bacillary / Q000517:prevention & control*; D004758:Enterobactin / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D021122:Protein Subunits / Q000235:genetics; D022621:Shiga Toxin / Q000235:genetics; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D012762:Shigella dysenteriae / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects* / Q000819:agonists / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D021122:Protein Subunits; C493898:Shiga toxin subunit A; D022281:Shigella Vaccines; D014157:Transcription Factors; D014613:Vaccines, Attenuated; C058483:virG protein, Shigella flexneri; D004758:Enterobactin; D022621:Shiga Toxin