A Phase 2 controlled human infection trial (NCT04242264) of WRSs2, a live-attenuated oral Shigella sonnei vaccine, has reported 89% protective efficacy the highest ever recorded for a Shigella vaccine candidate with no serious adverse events.
Written By: Anamika Koshti, Pharm D
Reviewed By: Pharmacally Editorial Team
On July 1, 2026, Cincinnati Children’s Hospital Medical Center announced results from a National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase 2 clinical trial (NCT04242264) of WRSs2, an investigational live-attenuated oral vaccine against Shigella sonnei, published in The Lancet Infectious Diseases. Two doses of the vaccine provided 89% protection against Shigella sonnei infection compared with placebo, surpassing efficacy levels reported in any previous Shigella vaccine trial and marking a pivotal advance in a field that has pursued a licensed vaccine for over a century.
Why a Shigella Vaccine Matters?
Shigella is a highly contagious bacterium spread through contaminated food, water, and direct person-to-person contact, causing severe diarrheal disease worldwide. Globally, it infects tens of millions of people each year and is responsible for hundreds of thousands of deaths, with children aged one to five bearing the greatest burden of illness. In the United States alone, an estimated 450,000 infections occur annually, resulting in over 5,000 hospitalizations and dozens of deaths. The situation is further complicated by rising antibiotic resistance, which is narrowing treatment options. Despite more than 100 years of research effort, no licensed Shigella vaccine exists to date.
The encouraging findings were generated using a Controlled Human Infection Model (CHIM), an established clinical research approach in which carefully screened healthy adult volunteers are intentionally exposed to the study pathogen under close medical supervision to evaluate vaccine efficacy.
Trial Design
The Phase 2 study enrolled 108 healthy adults between 18 and 49 years of age, with enrollment running from October 11, 2022, to January 9, 2024. Of these, 73 participants completed the controlled human infection (challenge) phase, in which vaccinated and placebo recipients were deliberately exposed to Shigella sonnei to assess protective efficacy. Participants in the challenge phase were intentionally exposed to a virulent Shigella sonnei challenge strain under carefully controlled clinical conditions, allowing investigators to directly measure the vaccine’s protective efficacy. WRSs2 is a live but weakened (attenuated) form of the bacteria, designed to stimulate an immune response without causing full-blown disease. The trial assessed both the safety and protective efficacy of the two-dose regimen.
Trial Results
Two doses of WRSs2 delivered 89% protection against Shigella sonnei infection compared to placebo, the highest efficacy reported for any Shigella vaccine candidate. The findings represent one of the strongest clinical efficacy signals reported to date for an oral live-attenuated Shigella vaccine and provide important evidence supporting continued clinical development of WRSs2. Beyond preventing infection, vaccinated participants who did develop symptoms experienced mild illness and lower levels of bacterial shedding, suggesting the vaccine may also reduce onward transmission. The safety data were reassuring, while some participants encountered short-lived side effects that prompted dosing refinements during the study, not a single serious adverse event was attributed to the vaccine. A small number of participants experienced temporary side effects, which led to dosing adjustments during the trial, supporting an overall favorable safety profile.
Researcher Perspective
Robert Frenck, MD, a pediatrician, professor in the Division of Infectious Diseases, and Director of the Vaccine Research Center at Cincinnati Children’s, served as a joint senior author of the study. He noted that these findings represent a meaningful step toward a safe and effective Shigella vaccine and that continued research holds real potential to reduce the global disease burden, especially in children. The study also involved contributions from Emory University’s Hope Clinic, the National Institute of Allergy and Infectious Diseases (NIAID), Walter Reed Army Institute of Research, the Naval Medical Research Command, and the Emmes Co., with funding provided by the National Institutes of Health and the U.S. Department of Defense.
Because this was a controlled human infection study conducted in healthy adults, larger field trials in populations at greatest risk, particularly young children living in Shigella-endemic regions, will be essential to confirm the vaccine’s effectiveness, durability of protection, and broader public health impact.
What This Means and What Comes Next?
For the millions of people, particularly children in endemic regions, who face repeated Shigella infections with diminishing treatment options due to antibiotic resistance, an effective oral vaccine would be transformative. These Phase 2 results provide the clearest signal yet that WRSs2 can deliver meaningful protection. The research team has stated that the findings support advancing WRSs2 into larger clinical trials, with a focus on high-risk populations including children in endemic regions. Future studies will also examine long-term protection, refine the optimal dosing regimen, and explore broader coverage against multiple Shigella strains beyond sonnei.
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About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.