To evaluate the efficacy and safety of a two-dose, live-attenuated oral vaccine candidate (WRSs2) against Shigella sonnei in healthy adults.
Approach:
Study Design: Phase 2, double-blind, randomized, placebo-controlled trial conducted at Cincinnati Children's Hospital Medical Center and the Hope Clinic of the Emory Vaccine Center.
Participants: 108 adults aged 18 to 49 with little existing immunity to S. sonnei were enrolled.
Vaccine Administration: Participants received either two doses of the vaccine, one placebo followed by one vaccine dose, or two placebo doses, given 28 days apart.
Exposure and Assessment: 28 days after the second dose, participants were exposed to S. sonnei, and shigellosis was assessed based on predefined criteria.
Key Findings:
Vaccine efficacy was 89% (95% CI, 71%-96%; P<.0001) with shigellosis occurring in 9% of vaccine recipients versus 81% of placebo recipients.
Severe shigellosis occurred in 3% of vaccine recipients compared to 69% of placebo recipients.
Vaccinated participants had lower bacterial shedding (53% vs. 88%) and lower peak stool bacterial loads.
Common side effects included headache (59%), fatigue (53%), diarrhea (45%), and stomach pain (36%).
Interpretation:
Limitations:
Small sample size and protocol changes during the study.
Results may not be generalizable to children or endemic settings.
