title: Safety and immunogenicity of SC599, an oral live attenuated Shigella dysenteriae type-1 vaccine in healthy volunteers: results of a Phase 2, randomized, double-blind placebo-controlled trial.
abstract: SC599 vaccine is a live Shigella dysenteriae 1 strain attenuated by deletion of invasion [icsA], iron chelation [ent, fep] and shiga toxin A subunit [stxA] genes. In a preliminary Phase 1 single dose prospective study, we showed that SC599 vaccine was well tolerated, and the maximum tolerable dose was greater than 10(8) CFU [Sadorge C, Ndiaye A, Beveridge N, Frazer S, Giemza R, Jolly N, et al. Phase 1 clinical trial of live attenuated Shigella dysenteriae type-1 DeltaicsA Deltaent Deltafep DeltastxA:HgR oral vaccine SC599 in healthy human adult volunteers. Vaccine 2008; 26(7):978-8]. In this Phase 2 trial, three groups of volunteers ingested a single dose of SC599 [10(5) CFU, n=38; 10(7) CFU, n=36] or placebo [n=37]. Both 10(5) and 10(7) CFU doses were immunogenic, inducing significant IgA and IgG LPS-specific ASCs and antibody responses, comparable in magnitude to those of other strains that prevented illness following experimental challenge. In the intention to treat analysis, 34.2% and 44.4% IgA ASC responders were detected in the 10(5) and 10(7) CFU groups respectively (p<0001 vs placebo for both groups), as well as 31.6% and 33.3% serum IgA responders (p<001 and p<0.001 vs placebo for 10(5) and 10(7) CFU groups, respectively). No difference between the two vaccine groups was observed. No stxB-specific antibody response was detected in the vaccines. SC599 excretion occurred in 23.7 and 30.6% of subjects in the 10(5) and 10(7) CFU groups, respectively. SC599 vaccine was well tolerated, and the reported adverse events were mainly digestive. These results indicate that a single oral immunization of SC599 vaccine elicits a significant circulating IgA ASC and serum antibody response that may confer protection against the most severe symptoms of Shigellosis in responders to the vaccine.
authors.affiliation: Université Paris Descartes, INSERM, Assistance Publique-Hôpitaux de Paris, CIC de Vaccinologie Cochin Pasteur (CIC BT505), Groupe Hospitalier Cochin-Saint Vincent de Paul, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.forename: Christine
authors.initials: C
authors.lastname: Sadorge
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jolly
authors.forename: Béatrice
authors.initials: B
authors.lastname: Poirier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Béchet
authors.forename: Diane
authors.initials: D
authors.lastname: van der Vliet
authors.forename: Valérie
authors.initials: V
authors.lastname: Seffer
authors.forename: Nicola
authors.initials: N
authors.lastname: Fenner
authors.forename: Kelly
authors.initials: K
authors.lastname: Dowling
authors.forename: Raphaela
authors.initials: R
authors.lastname: Giemza
authors.forename: Julie
authors.initials: J
authors.lastname: Johnson
authors.forename: Anna
authors.initials: A
authors.lastname: Ndiaye
authors.forename: Muriel
authors.initials: M
authors.lastname: Vray
authors.forename: Philippe
authors.initials: P
authors.lastname: Sansonetti
authors.forename: Philippe
authors.initials: P
authors.lastname: Morand
authors.forename: Claire
authors.initials: C
authors.lastname: Poyart
authors.forename: David
authors.initials: D
authors.lastname: Lewis
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Gougeon
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D022281:Shigella Vaccines / Q000009:adverse effects* / Q000276:immunology*; D012762:Shigella dysenteriae / Q000235:genetics* / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010919:Placebos; D022281:Shigella Vaccines; D014613:Vaccines, Attenuated