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 Δ icsA Δ ent Δ fep Δ stxA :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 p p 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.