An experimental vaccine developed by the Walter Reed Army Institute of Research achieved 89% efficacy in preventing shigellosis during a clinical trial published in The Lancet Infectious Diseases, offering a potential breakthrough against a leading global cause of severe childhood diarrheal disease and antibiotic resistance.
Diarrhea remains an enduring public health crisis globally, claiming more than 1 million lives each year. Nearly half of those who die are children under the age of five, with Chad recording the highest rate of childhood mortality at roughly one in 140 children under five dying annually. Despite the immense toll, public health advocates note that the condition often suffers from a lack of attention driven by social discomfort, a phenomenon researchers refer to as the poo taboo
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Now, human trial results for an experimental vaccine designated as WRSs2 offer a significant countermeasure. Developed from a weakened version of the Shigella bacteria suspended in a liquid format similar to yogurt, the vaccine is administered twice over a month in doses slightly smaller than a shot glass. The findings were published in The Lancet Infectious Diseases this summer, demonstrating 89% efficacy against shigellosis.
Rigorous Testing Protocol and Trial Design
The clinical evaluation recruited 108 adult volunteers who were split evenly between the experimental vaccine and a placebo of salt water. The trial was conducted jointly at Cincinnati Children’s Hospital Medical Center and the Emory Vaccine Center’s Hope Clinic in Atlanta. Dr. Robert Frenck, a professor of pediatrics at Cincinnati Children’s and director of its Center for Vaccine Research, co-led the study and explained that the weakened bacteria is engineered to provoke an immune response without causing severe illness.
Volunteers were compensated approximately $250 a day for roughly a week and completed comprehension quizzes to ensure they understood the protocols. Rather than enrolling thousands of participants and waiting for natural infections to occur, researchers used a deliberate exposure model to test the vaccine’s protective capacity. Dr. Kawsar Talaat, an infectious disease physician and vaccine scientist at the Johns Hopkins Bloomberg School of Public Health who was not involved in the trial, described the methodology as a brutal test.
“setup also makes the 89% figure harder to shrug off, says Dr. Kawsar Talaat, an infectious disease physician and vaccine scientist at the Johns Hopkins Bloomberg School of Public Health. Deliberate exposure is a brutal test — in this trial, 81% of the placebo group got sick, experiencing diarrhea and fever in some cases before receiving antibiotics.”
Dr. Kawsar Talaat, Johns Hopkins Bloomberg School of Public Health
Talaat noted that preventing almost 90% of the illness under such rigorous conditions represents the best efficacy observed for a Shigella vaccine candidate to date.
The Toll of Shigellosis and Obstacles to Treatment
Shigella spreads primarily through contaminated food and water, thriving in environments marked by poor sanitation. Globally, diarrheal illness ranks as the second leading cause of childhood death, and Shigella stands out as a predominant bacterial driver. Surviving children frequently face long-term consequences. Dr. Jahangir Hossain of the Gambia Medical Research Council Unit at the London School of Hygiene & Tropical Medicine pointed out that affected children frequently fall off their normal growth trajectories.
Children who contract Shigella often experience prolonged diarrhea, elevated hospitalization rates, increased malnutrition, and cognitive impairment. The peak risk window occurs between 12 and 23 months of age. Hossain, who has spent decades studying the disease across Bangladesh and West Africa, noted that clinical centers can be hours away for rural families, and local diagnostic laboratories are frequently lacking.
Treatment relies primarily on antibiotics, but antimicrobial resistance has exceeded 80% for some antibiotics in specific regions, causing treatment efficacy to fluctuate widely.
Historical Context and Next Steps for Vaccine Development
Despite more than a century of scientific research, no Shigella vaccine has ever been successfully licensed for public use. Prior candidates fell well short of the benchmarks set by WRSs2. An earlier precursor, WRSs1, demonstrated only 40% efficacy alongside increased side effects. Other candidates included an Israeli vaccine that managed 28% overall protection, and another formulation that reached 74% in young adults but failed to protect younger children.
While the World Health Organization typically looks for an efficacy benchmark of around 60% for public health deployment, the new candidate’s 89% effectiveness has generated considerable optimism among specialists. However, researchers emphasize that caution remains warranted given the preliminary nature of the adult data.
Hossain highlighted that the trial was small and limited to adults, underscoring the necessity for larger, expanded studies to determine whether the vaccine can provide safe and effective protection in young children living in endemic areas.
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