Clinical Trial of Shigella Vaccine Shows 89% Protection

Cincinnati Children's researchers help lead study to combat disease that poses global health risk

CINCINNATI, July 1, 2026 /PRNewswire/ --A new clinical trial involving researchers from Cincinnati Children's reports encouraging progress toward a long-sought vaccine against Shigella, a leading cause of diarrheal disease worldwide.

Children 1 to 5 years old make up most cases of Shigella, often becoming very sick or even dying. Every year, Shigella infects tens of millions of people worldwide and causes hundreds of thousands of deaths. In the United States, an estimated 450,000 Shigella infections occur annually, with over 5,000 people hospitalized and dozens dying.

The highly contagious bacteria—spread through fecal waste that contaminates water or food as well as person-to-person contact—is increasingly difficult to treat because of growing antibiotic resistance.

Despite over 100 years of research, no licensed Shigella vaccine currently exists—making these findings especially significant. 

Published online in The Lancet Infectious Diseases, the new study evaluated an oral vaccine candidate called WRSs2. The vaccine was designed to protect against Shigella sonnei – a type of bacteria more often seen in higher-income countries, where outbreaks can be linked to international travel, military deployments, childcare settings, and other high‑risk groups.

Two doses of WRSs2 provided 89% protection against Shigella sonnei compared with placebo, the researchers stated. That substantially exceeded efficacy reported in previous Shigella vaccine trials. 

The findings of the new study support advancing WRSs2 into larger clinical trials, including studies in high-risk populations such as children in endemic regions. Future research will focus on long-term protection, optimal dosing and broader coverage against multiple Shigella strains.

A leading research role

Cincinnati Children's researchers played a leading role in the new study. Robert Frenck, MD, a pediatrician who is a professor in the Division of Infectious Diseases and director of the health system's Vaccine Research Center, served as a joint senior author and contributed to study design, clinical oversight and funding acquisition. Other Cincinnati Children's contributors included: Michelle Dickey, NP (clinical investigation); Christina Quigley, PhD (methodology and data validation); Tena Pham, RN (clinical conduct); Josh Adams, BS (data collection); and Gaurav Kwatra, PhD (research and analysis). 

"This study represents an important step forward in developing a safe and effective vaccine against Shigella," Frenck says. "With continued research, we have the potential to significantly reduce the global burden of this disease, particularly among children."

Promising early results

WRSs2 is a live-attenuated Shigella sonnei vaccine candidate that has previously shown safety and the ability to trigger an immune response. In this trial, researchers evaluated its safety and efficacy in a controlled human infection model. 

The phase 2 trial enrolled 108 healthy adults, who were 18 to 49 years old, between Oct. 11, 2022, and Jan. 9, 2024. Seventy-three participants completed the controlled infection (challenge) phase used to test vaccine protection.

The WRSs2 vaccine uses a live but weakened form of the bacteria to stimulate immune protection without causing full disease. In addition to reducing illness, vaccinated participants experienced less severe symptoms and lower levels of bacterial shedding, suggesting the vaccine may also help curb transmission. 

What's next?

Although the results are promising, researchers emphasized the need for further optimization. A small number of participants experienced temporary side effects, which led to adjustments in dosing during the trial. Importantly, no vaccine-related serious adverse events were reported, supporting a favorable safety profile. 

The WRSs2 vaccine is not yet commercially manufactured, but instead is being developed through collaborations among government, military and academic research teams as it advances through clinical trials.

About the study

Funding was provided by the National Institutes of Health with pharmaceutical support from the U.S. Department of Defense. 

Other contributing institutions included Emory University (Hope Clinic of the Emory Vaccine Center), National Institute of Allergy and Infectious Diseases, the Emmes Co., Walter Reed Army Institute of Research, and the Naval Medical Research Command.

SOURCE Cincinnati Children's Hospital Medical Center