An investigational vaccine candidate for Shigella provided high-level protection in a phase 2 clinical trial, researchers reported last week in The Lancet Infectious Diseases.
In a challenge trial conducted at two US sites, 73 healthy adults aged 18 to 49 were randomly assigned to receive WRS2, a live-attenuated oral vaccine targeting Shigella sonnei, or placebo. S sonnei is one of four species of the highly contagious bacteria, which infects tens of millions around the world, causing mild to severe diarrhea and vomiting. There are no licensed vaccines for any of the Shigella species, two of which—S sonnei and S flexneri—are becoming increasingly resistant to first-line antibiotics.
The primary end point of the trial was occurrence of shigellosis following an oral challenge with S sonnei, assessed from day 57 to day 63 after the challenge in participants who received two doses with two different dose levels and the placebo recipients. Investigators also assessed systemic adverse events.
89% estimated vaccine efficacy
Among the 34 participants given the pooled two-dose vaccine, three (9%) were diagnosed as having shigellosis, compared with 21 (81%) of 26 placebo recipients, yielding an estimated vaccine efficacy of 89%. Participants in both two-dose groups elicited strong antibody response. Although most adverse events were mild, six vaccine recipients experienced grade 3–level adverse events, which prompted a review by the data safety monitoring board and a reduction of the vaccine dose.
The investigators say the next step will be to optimize the dose level and conduct larger trials in endemic settings that include children, who are among the most affected by shigellosis in high-burden settings like sub-Saharan Africa.
“This study represents an important step forward in developing a safe and effective vaccine against Shigella,” senior study author Robert W. Frenck, Jr., MD, director of the Vaccine Research Center at Cincinnati Children’s Hospital, said in a news release. “With continued research, we have the potential to significantly reduce the global burden of this disease, particularly among children.”
