This is a double-blind placebo-controlled randomized-study trial to test the safety, reactogenicity, immunogenicity and efficacy of a 10^6 cfu dose of an oral live-attenuated S. sonnei vaccine candidate, WRSs2, in up to 120 healthy males and non-pregnant females aged 18-49, inclusive. This is a two-phase study, an outpatient WRSs2 vaccination phase and an inpatient S. sonnei 53G challenge phase. Subjects will be randomized 1:1:1 into one of three vaccination arms. Outpatient WRSs2 phase: Arm 1 will receive two doses of WRSs2 vaccine; Arm 2 will receive one dose of placebo and one dose of WRSs2 vaccine; Arm 3 will receive two doses of placebo. All three arms will then be admitted to an inpatient unit and given one dose of S. sonnei 53G challenge. The study will be conducted in up to 3 Vaccine Treatment Evaluation Units (VTEU) sites. The study duration is approximately 24 months with subject participation duration approximately 8 months. The Primary Objective of this study is to estimate vaccine efficacy of 1 and 2 doses of WRSs2 in preventing shigellosis, following challenge with S. sonnei strain 53G. The Secondary Objectives are to:1) Evaluate the safety of 1 and 2 doses of WRSs2; 2) Evaluate immune responses following vaccination (immunogenicity) with 1 and 2 doses of WRSs2 and after challenge with S. sonnei strain 53G by serum anti-LPS and anti-Invaplex IgG and IgA by ELISA; 3) Determine fecal shedding of S. sonnei after WRSs2 vaccination and 53G challenge by qualitative stool culture.
This is a trial to evaluate the safety, reactogenicity, immunogenicity and efficacy of a 10^6 cfu dose of an oral live-attenuated S. sonnei vaccine candidate, WRSs2, in up to 120 healthy males and non-pregnant females aged 18-49, inclusive. This is a two-phase study, an outpatient WRSs2 vaccination phase and an inpatient S. sonnei 53G challenge phase. Subjects will be randomized 1:1:1 into one of three vaccination arms. Outpatient WRSs2 phase: Arm 1 will receive two doses of WRSs2 vaccine; Arm 2 will receive one dose of the placebo and one dose of WRSs2 vaccine; Arm 3 will receive two doses of the placebo. All three arms will then be admitted to an inpatient unit and given one dose of S. sonnei 53G challenge. The study will be conducted in up to 3 Vaccine Treatment Evaluation Units (VTEU) sites. The study duration is approximately 24 months with subject participation duration approximately 8 months. The Primary Objective of this study is to estimate vaccine efficacy of 1 and 2 doses of WRSs2 in preventing shigellosis, following challenge with S. sonnei strain 53G.