Shigella Vaccine Shows Promise in Phase 2 Human Challenge Trial

Key Takeaways

• Pooled two-dose vaccination was associated with an estimated 89% efficacy against shigellosis after oral challenge.
• Most adverse events were mild, but six vaccine recipients had grade 3-level events that triggered review and dose reduction.
• Investigators said dose optimization will precede larger endemic-setting trials that include children.

WRS2, a live-attenuated oral vaccine against Shigella sonnei, showed an estimated 89% efficacy in a phase 2 human challenge trial in healthy adults. The candidate was tested after controlled oral challenge rather than in an endemic field setting, so the finding reflects a defined experimental model.

The trial enrolled 73 healthy adults aged 18 to 49 at two US sites and randomly assigned them to WRS2 or placebo. After vaccination, participants underwent oral challenge with S sonnei within the controlled study design. The primary endpoint was shigellosis from day 57 to day 63 after challenge, and researchers also assessed systemic adverse events. Participants in both two-dose groups also elicited strong antibody response during the study period. The findings reflect performance in a challenge model rather than protection measured in endemic populations.

Efficacy was reported for the pooled two-dose comparison against placebo after challenge. In that analysis, 3 of 34 participants in the vaccine group developed shigellosis, compared with 21 of 26 placebo recipients. Those outcomes yielded the reported vaccine efficacy estimate of 89% for the pooled two-dose regimen. Illness rates were lower with vaccination in this healthy adult challenge study.

Most adverse events were mild overall across the trial. Six vaccine recipients, however, experienced grade 3-level adverse events during follow-up after vaccination. Those events prompted data safety monitoring board review and a subsequent reduction in vaccine dose. The dosing plan was adjusted after that review.

Investigators said the next step is dose optimization followed by larger trials in endemic settings that include children. No licensed vaccines exist for any Shigella species, leaving a persistent developmental gap. S sonnei and S flexneri are becoming increasingly resistant to first-line antibiotics, while children remain heavily affected in high-burden settings such as sub-Saharan Africa. The immediate focus remains dose refinement before broader endemic-setting evaluation. The development path now points to larger studies in pediatric populations.