To evaluate the efficacy and safety of a live-attenuated oral Shigella sonnei vaccine candidate in a controlled human infection trial.
Approach:
Trial Design: A double-blind, randomized, placebo-controlled trial was conducted involving 108 healthy adults aged 18 to 49 years at two US centers.
Vaccine Administration: Participants received two oral doses of WRSs2 at either 10⁶ or 5 × 10⁵ colony-forming units, a single 10⁶-colony-forming-unit dose, or placebo.
Challenge and Efficacy Assessment: Twenty-eight days after vaccination, 73 participants underwent oral challenge with virulent S. sonnei to assess vaccine efficacy.
Key Findings:
Shigellosis developed in 3 of 34 vaccinated participants (9%) compared to 21 of 26 placebo recipients (81%).
Severe shigellosis occurred in 1 vaccinated participant versus 18 in the placebo group.
Postchallenge bacterial shedding was lower in vaccinated participants (53%) compared to placebo (88%), with shorter shedding duration and lower bacterial counts.
Interpretation:
Limitations:
The study excluded participants with a BMI greater than 40 kg/m² or those using weight-loss medications.
Long-term effects and the impact on transmission remain to be determined.
