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 t...

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Veröffentlicht in:Vaccine 2009-02, Vol.27 (8), p.1184-1191
Hauptverfasser: Launay, Odile, Sadorge, Christine, Jolly, Nathalie, Poirier, Béatrice, Béchet, Stéphane, van der Vliet, Diane, Seffer, Valérie, Fenner, Nicola, Dowling, Kelly, Giemza, Raphaela, Johnson, Julie, Ndiaye, Anna, Vray, Muriel, Sansonetti, Philippe, Morand, Philippe, Poyart, Claire, Lewis, David, Gougeon, Marie-Lise
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Sprache:eng
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Zusammenfassung: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 108 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 [105 CFU, n = 38; 107 CFU, n = 36] or placebo [ n = 37]. Both 105 and 107 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 105 and 107 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 105 and 107 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 105 and 107 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.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2008.12.021