A live-attenuated oral Shigella sonnei vaccine candidate demonstrated an estimated 89% efficacy against shigellosis in a phase 2 controlled human infection trial, offering strong evidence of protection in this controlled challenge model. The findings, published in The Lancet Infectious Diseases, also showed reduced bacterial shedding after challenge, although whether this would reduce transmission remains to be determined.

“Despite long-standing research, no licensed vaccine exists for Shigella, a leading cause of bacterial diarrhea and dysentery,” wrote Nadine Rouphael, MD, Emory University, and colleagues.

Researchers conducted a double-blind, randomized, placebo-controlled trial at two US centers involving 108 healthy adults aged 18 to 49 years. 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. Following a safety review, later participants were randomized to the lower-dose two-dose regimen or placebo. Twenty-eight days after the final vaccination, 73 participants underwent oral challenge with virulent S. sonnei.

Shigellosis developed in 3 of 34 participants (9%) who received the pooled two-dose vaccine regimens compared with 21 of 26 placebo recipients (81%), corresponding to an estimated vaccine efficacy of 89%. Severe shigellosis occurred in 1 vaccinated participant compared with 18 placebo recipients. Postchallenge bacterial shedding occurred in 53% of pooled two-dose vaccine recipients compared with 88% of placebo recipients, with vaccinated participants experiencing shorter shedding duration and bacterial counts approximately 10-fold lower than the placebo group.

Both two-dose regimens elicited robust systemic antibody responses after the first vaccination, with little additional immune boosting after the second dose, a finding that may inform future dose optimization. Six participants experienced grade 3 adverse events that prompted independent safety reviews, dose reduction, and revised eligibility criteria that excluded participants with BMI greater than 40 kg/m² or use of weight-loss medications. Most adverse events were mild to moderate, and no vaccine-related serious adverse events or deaths occurred.

“These results lay the groundwork for advancing this candidate towards licensure and broader implementation to reduce the global burden of shigellosis,” the researchers concluded.

Disclosures: Nadine Rouphael, MD, and several coauthors reported research funding and other relationships with government agencies and vaccine manufacturers in the original study; all other authors declared no competing interests.

Source: The Lancet Infectious Diseases