[Show abstract][Hide abstract] ABSTRACT: Orally delivered, inactivated whole-cell vaccines are safe methods of inducing local and systemic immunity. To increase surface proteins associated with adherence and invasion, Shigella sonnei were grown in BHI broth containing deoxycholate. A whole-cell vaccine (SsWC) was then produced by formalin inactivation. In pre-clinical studies, the SsWC vaccine was immunogenic and protected against S. sonnei-induced keratoconjunctivitis in the guinea pig model. In a randomized, double-blind, placebo-controlled, Phase I study, 10 evaluable subjects received either three doses of SsWC on Days 0, 14, and 28 (N = 3); five doses of SsWC on Days 0, 2, 4, 6, and 28 (N = 4); or placebo (N = 3). Each dose contained 2.0 x 10(10) inactivated cells. Serum and fecal antibodies against SsWC, LPS, and IpaC were measured by ELISA. A > or = 4-fold increase in titer was considered significant. Both SsWC dosing regimens were well tolerated. No fever or severe gastrointestinal symptoms were noted by any of the vaccinated subjects. Antibody responses were similar in the two dosing groups. Serum IgG or IgA responses to SsWC were seen in six of seven vaccinees (86%), to LPS in four of seven (57%), and to IpaC in five of seven (61%). Fecal IgA responses to these three antigens developed in five of five, three of five, and three of five subjects, respectively. Among the seven vaccinees, geometric mean rises in serum IgA levels to all three immunogens were significant; IgG increases trended toward significance (paired one-tailed t-test). We conclude that SsWC was immunogenic and protective in animal studies and well tolerated and immunogenic in a Phase I trial.