A promising investigational vaccine for Shigella bacteria has demonstrated high-level protection in a phase 2 clinical trial, as reported recently in The Lancet Infectious Diseases.
The challenge trial, conducted at two U.S. sites, involved 73 healthy adults aged 18 to 49. Participants were randomly assigned to receive either WRS2, an oral live-attenuated vaccine targeting Shigella sonnei, or a placebo. S. sonnei is one of four species of this highly contagious bacterium, responsible for infecting tens of millions globally and causing symptoms ranging from mild to severe diarrhea and vomiting. Currently, there are no licensed vaccines available for any Shigella species. Compounding the issue, two species, S. sonnei and S. flexneri, are showing increasing resistance to common first-line antibiotics.
The trial’s primary objective was to determine the occurrence of shigellosis after participants were orally challenged with S. sonnei. This assessment took place between day 57 and day 63 after the challenge in individuals who received two doses of the vaccine at different levels or the placebo. Investigators also monitored for systemic adverse events.
Estimated Vaccine Efficacy at 89%
Out of the 34 participants who received the pooled two-dose vaccine, only three (9%) were diagnosed with shigellosis. In contrast, 21 out of 26 placebo recipients (81%) developed the illness, resulting in an estimated vaccine efficacy of 89%. Participants in both two-dose vaccine groups exhibited a robust antibody response. While most reported adverse events were mild, six vaccine recipients experienced grade 3 adverse events. These events prompted a review by the data safety monitoring board and led to a reduction in the vaccine’s dosage.
Researchers plan to optimize the dosage levels and proceed with larger trials in areas where shigellosis is endemic. These future studies will include children, who are disproportionately affected by shigellosis in high-burden regions like sub-Saharan Africa.
"This study marks a significant advancement in the development of a safe and effective vaccine against Shigella," stated senior study author Robert W. Frenck, Jr., MD, director of the Vaccine Research Center at Cincinnati Children’s Hospital, in a news release. "Through ongoing research, we have the potential to substantially decrease the global impact of this disease, particularly among children."