Phase 1 clinical trial of live attenuated Shigella dysenteriae type-1 DeltaicsA Deltaent Deltafep DeltastxA:HgR oral vaccine SC599 in healthy human adult volunteers.
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.
Sadorge
Christine
C
Centre de Recherche Vaccinale et Biomédicale, Institut Pasteur, 75724 Paris Cedex 15, France.
Ndiaye
Anna
A
Beveridge
Nathalie
N
Frazer
Schale
S
Giemza
Rafaela
R
Jolly
Nathalie
N
Johnson
Julie
J
Liddy
Helen
H
Cosgrove
Catherine A
CA
Allavena
Paola
P
Mantovani
Alberto
A
Béchet
Stéphane
S
Fontaine-Thompson
Annick
A
Griffin
George E
GE
Dupont
Francis
F
Sansonetti
Philippe J
PJ
Lewis
David J M
DJ
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*
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