A vaccine candidate developed by the Walter Reed Army Institute of Research has demonstrated 89% effectiveness against shigellosis, one of the leading causes of diarrheal deaths worldwide, as thousands of Americans battle explosive diarrhea from a Cyclospora outbreak linked to tainted lettuce this summer. The breakthrough comes as Michigan confirmed the first two deaths from the current outbreak.
The vaccine, called WRSs2, represents a potential market solution to a global health crisis that kills over 1 million people annually from diarrheal illness such as dysentery. Nearly half of those deaths are children under age 5. Chad has the highest rate of childhood deaths, with roughly 1 in 140 children under 5 dying each year.
The Trial Results
Researchers at Cincinnati Children's Hospital Medical Center and the Emory Vaccine Center's Hope Clinic in Atlanta tested the vaccine on 108 adults. Half received the vaccine—a weakened version of the shigella bacteria suspended in a liquid, almost like a yogurt, in a dose a tad less than a shot-glass worth taken twice a month apart. The other half got doses of salt water. The results, published in The Lancet Infectious Diseases this summer, showed remarkable efficacy.
Dr. Robert Frenck, a professor of pediatrics at Cincinnati Children's and director of its Center for Vaccine Research, co-led the trial. He said the weakened bacteria is strong enough to bring on an immune reaction but shouldn't make anyone really sick. The trial's design involved deliberate exposure to the disease, making the results particularly significant. Dr. Kawsar Talaat, an infectious disease physician and vaccine scientist at the Johns Hopkins Bloomberg School of Public Health, said 81% of the placebo group got sick, experiencing diarrhea and fever in some cases before receiving antibiotics. "So the fact that the vaccine prevented almost 90% of the illness is really remarkable," Talaat said. "It's the best efficacy we've ever seen."
Frenck said the volunteers were paid about $250 a day for roughly a week and took a quiz to ensure they knew the risks. Their commitment made a swift and efficient trial possible. "Throughout the world, diarrheal illness is the second leading cause of death of children," Frenck said. "And Shigella is one of the more common causes of bacterial diarrhea." It spreads through contaminated food and water and is more common where sanitation is poor.
The Disease's Devastating Impact
Dr. Jahangir Hossain of the Gambia Medical Research Council Unit at the London School of Hygiene & Tropical Medicine said children who get Shigella often slip off their growth curves and never fully recover. "If somebody develops Shigella, then they develop prolonged diarrhea, more hospitalization, more malnutrition and cognitive impairment," he said. The peak risk arrives between 12 and 23 months of age.
Hossain said he has battled shigellosis since the 1990s, first in Bangladesh and now in West Africa. At the International Centre for Diarrhoeal Disease Research in Dhaka, sometimes 800 diarrheal patients would come in a day. "A Shigella patient comes with bloody diarrhea. They develop fever, and abdominal pain," Hossain said. "Definitely it is emotional for every doctor facing a patient coming with Shigella and malnutrition." He said families often travel one to three hours to reach a clinic and that diagnostic labs common in American hospitals mostly aren't there.
Antibiotic Resistance Makes Vaccine Critical
Treatment is antibiotics, but resistance has reached over 80% for some antibiotics in some regions. "The biggest problem is antimicrobial resistance," Hossain said, listing ciprofloxacin, azithromycin and ceftriaxone as antibiotics that are sometimes ineffective. Talaat said, "As these organisms become harder and harder to treat, the need for a vaccine also increases." She added, "We saw it with typhoid—there's some typhoid that's almost impossible to treat with antibiotics now." Vaccines could reduce antibiotic use and therefore resistant strains.
No Shigella vaccine has ever been licensed despite more than 100 years of research. Prior candidates topped out below WRSs2's efficacy: one had 74% in young adults but no protection in younger children, an Israeli vaccine managed 28% overall, and WRSs1 had 40% and more side effects. Hossain said, "It is very good efficacy," and added, "Usually WHO wants 60% efficacy and then it is fine—but it is 89% efficacy. It is a good hope." He cautioned that it was a small trial and only in adults.
The vaccine wasn't side-effect free. Over half of recipients reported a headache and about 45% had some diarrhea after their dose, but no one was hospitalized. The authors called the safety profile acceptable while noting more work is needed to balance safety and efficacy.
Next Steps and Combination Possibilities
WRSs2 protects against a single species, Shigella sonnei. Frenck said, "The holy grail—the thing that would be perfect—would be a vaccine that would control ETEC [enterotoxigenic E. coli], Campylobacter and Shigella," and said that would allow prevention with one or two administrations. A combination vaccine could also help because kids get a lot of vaccines. Talaat said it's easier to add one combination vaccine than several into the schedule, like MMR or Tdap. Hossain said, "Combination is good—if it's possible to make it in a realistic way," but warned that combining many serotypes and pathogens could be practically difficult. "We cannot delay—we need something immediately," he said.
All agreed the next step is testing in children. The paper and Hossain called for trials in places where poor sanitation contributes to high rates of diarrheal disease, especially among young children. Talaat said, "The most important population for a potential Shigella vaccine would be children under 5," and added, "We want a vaccine that's safe and effective in children as young as one year of age, or even younger." Frenck said vaccines are needed to achieve his goal of "really reducing deaths of children in the world."
Why This Matters:
This Army-developed vaccine represents a potential breakthrough in preventing a disease that disproportionately kills children in regions with poor sanitation infrastructure. The 89% efficacy rate exceeds WHO's 60% threshold and surpasses all previous attempts over a century of research. With antibiotic resistance reaching over 80% in some regions, market-based vaccine development offers a more sustainable solution than relying on increasingly ineffective pharmaceutical treatments. The current Cyclospora outbreak in the United States, which has already caused two deaths in Michigan, demonstrates that diarrheal diseases remain a threat even in developed nations with advanced healthcare systems. Successful deployment of this vaccine could reduce healthcare costs, prevent childhood cognitive impairment from malnutrition, and decrease reliance on antibiotics—addressing the growing crisis of antimicrobial resistance that threatens to make common infections untreatable.