A new vaccine candidate offers hope for millions afflicted by diarrhoea, which kills 1m people worldwide every year, with nearly half of them under five.
But in the world of public health, however, the disease often does not get the attention it deserves. It’s because of what researchers call the “poo taboo” – people just aren’t comfortable talking about diarrhoea, reports NPR.
‘Rigorous’ trial, ‘remarkable’ response
The new vaccine is called WRSs2, named after the Walter Reed Army Institute of Research. It was tested jointly at Cincinnati Children’s Hospital Medical Centre and the Emory Vaccine Centre’s Hope Clinic in Atlanta.
The results were published recently in The Lancet Infectious Diseases: it was 89% effective at preventing one of the leading causes of diarrhoeal deaths, shigellosis.
The study recruited 108 adults. Half received the vaccine, a weakened version of the Shigella bacteria suspended in a liquid – almost like a yogurt. The dose is a tad less than a shot-glass worth, taken twice a month apart. The other half got doses of salt water.
The weakened bacteria is strong enough to bring on an immune reaction but shouldn’t make anyone really sick, says Dr Robert Frenck, a professor of paediatrics at Cincinnati Children’s and director of its Centre for Vaccine Research, who co-led the trial.
Even though the number of trial participants were relatively small, that “rigorous” set up 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 diarrhoea and fever in some cases before receiving antibiotics.
“So the fact that the vaccine prevented almost 90% of the illness is really remarkable,” she says. “It’s the best efficacy we’ve ever seen.”
Talaat runs studies of her own but was not involved in this trial.
Frenck adds they were grateful to the volunteers who contributed to the study: they were paid about $250 a day for roughly a week for the trial, and took a quiz ensuring they knew the risks.
While it might not be for everyone, he says they made a swift and efficient trial possible rather than enrolling thousands and waiting for them to naturally get infected – and their commitment is critical to the vaccine effort.
A scourge for children
“Throughout the world, diarrhoeal illness is the second leading cause of death of children,” he says. “And Shigella is one of the more common causes of bacterial diarrhoea.
It’s spread through contaminated food and water. Cases are more common in areas with poor sanitation. The children who survive don’t always recover fully: they often slip off their growth curves and never quite catch up.
“If somebody develops Shigella, then they develop prolonged diarrhoea, more hospitalisation, more malnutrition and cognitive impairment,” says Dr Jahangir Hossain of the Gambia Medical Research Council Unit at the London School of Hygiene & Tropical Medicine. The peak of risk, he says, arrives between 12 and 23 months of age.
Hossain has spent his career battling shigellosis cases since the 1990s, first in Bangladesh and now in West Africa. At the International Centre for Diarrhoeal Disease Research in Dhaka, where he started out, sometimes 800 diarrhoeal patients would come in a day, he says.
“A Shigella patient comes with bloody diarrhoea. They develop fever, and abdominal pain,” he says. “Definitely it is emotional for every doctor facing a patient coming with Shigella and malnutrition.”
Families often travel one to three hours to reach a clinic, he says, and the diagnostic labs American hospitals take for granted mostly aren’t there. The treatment is antibiotics, but with resistance reaching more than 80% for some antibiotics in some regions, efficacy can vary widely.
No Shigella vaccine has ever been licensed, despite more than 100 years of research. Prior candidates topped out well below WRSs2’s efficacy: one had 74% in young adults but no protection in younger children; an Israeli vaccine managed 28% overall; WRSs2’s precursor, WRSs1, had 40% and more side effects.
“It is very good efficacy,” Hossain says. “Usually WHO wants 60% efficacy and then it is fine – but it is 89% efficacy. It is a good hope.”
But he sounds a cautionary note about the study: “It is a small trial, and it is only the adult age group.” Hossain wants to see larger trials happen and see if it works in young children.
A timely trial
Hossain notes that the prospect of a vaccine is especially critical because increasing antibiotic resistance has complicated shigellosis treatment.
“The biggest problem is antimicrobial resistance. Usually we give antibiotics – ciprofloxacin, then azithromycin, and ceftriaxone – but sometimes it does not work. In some countries, especially in South Asia, even ceftriaxone is resistant.”
Patients with antibiotic resistant Shigella, therefore, are often sick longer and are at higher risk of dying.
Talaat sees the same trend and highlights a precedent for what a vaccine can do about it. “As these organisms become harder and harder to treat, the need for a vaccine also increases,” she says. “We saw it with typhoid – there’s some typhoid that’s almost impossible to treat with antibiotics now.”
She says if vaccines were to prevent the infection themselves, less antibiotics would be used, which would, in turn, decrease the amount of resistant strains.
The vaccine is not side-effect free. More than half reported a headache and about 45% of recipients had some diarrhoea after their dose. But no one was hospitalised from the vaccine.
The authors called the safety profile acceptable while noting more work will be done to hone its safety-efficacy balance – vaccines often have a trade-off of more side-effects with a higher dose for a stronger efficacy.
What's next
WRSs2 is protective against a single species, Shigella sonnei. While it’s one of the most common causes of diarrhoeal deaths, it’s part of a group of triggering bacteria.
“The holy grail – the thing that would be perfect – would be a vaccine that would control ETEC [enterotoxigenic E. coli], Campylobacter and Shigella,” Frenck says. “Then you’d be able to prevent all of these with one or two administrations.”
Frenck imagines a combination vaccine that would protect against all the major bacterial causes of diarrhoeal deaths, albeit probablt not cyclosporiasis.
There’s a practical reason for making it a combination vaccine too, Talaat says.
Children get a lot of vaccines, so Talaat says it’s easier to add one combination vaccine rather than several into the schedule – like the MMR or Tdap vaccine.
Hossain is more cautious about whether making it a combination will impede vaccine development.
“Combination is good, if it’s possible to make it in a realistic way,” he says. But he adds that these vaccine trials have been ongoing for decades and worries that if researchers “combine many serotypes and many pathogens together, it might be practically difficult”.
“We cannot delay. We need something immediately,” he urges.
Regardless of whether it is a combination vaccine or not, all agree the next step is making sure it works in children. The people who die of and are affected by shigellosis are overwhelmingly small children in the global south, who, the authors say, have poorer immunity than well-developed and nourished children.
The paper – like Hossain – calls for trials in places where poor sanitation is a factor in high rates of diarrhoeal disease, targeting particularly young children next.
“The most important population for a potential Shigella vaccine would be children under five,” Talaat says. “We want a vaccine that’s safe and effective in children as young as 12 months old, or even younger.”
For Frenck, that’s the whole point. He says vaccines are needed to achieve his goal of “really reducing the deaths of children in the world”.
Study details
Efficacy of WRSs2, a live-attenuated Shigella sonnei vaccine, against shigellosis in a controlled human infection model in the USA: a phase 2, double-blind, randomised, placebo-controlled trial
Nadine Rouphael, Shahida Baqar, Michelle Dickey et al.
Published in The Lancet on 30 June 2026
Summary
Background
Despite long-standing research, no licensed vaccine exists for shigella, a leading cause of bacterial diarrhoea and dysentery. WRSs2 is a live-attenuated Shigella sonnei vaccine candidate which has previously shown safety and immunogenicity. In this trial, we evaluated its safety and efficacy in a controlled human infection model.
Methods
In this phase 2, double-blind, randomised, placebo-controlled trial at two sites in the USA, healthy adults aged 18–49 were assigned using a site-stratified permuted-block schedule. The original three-arm design allocated participants 1:1:1 to two-dose WRSs2 (106 colony-forming units [CFU]), one-dose placebo followed by one-dose WRSs2 (106 CFU), or two-dose placebo; doses were given 28 days apart. After 69 participants were enrolled, a Data and Safety Monitoring Board (DSMB)-triggered safety review and protocol amendment resulted in subsequent participants being assigned 2:1 to two-dose WRSs2 (5 × 105 CFU) or placebo. Participants were challenged orally 28 days after the second vaccination with approximately 1·5 × 103 CFU of S sonnei 53G. The primary endpoint was endpoint review committee-adjudicated shigellosis in challenged participants. Safety was assessed in all vaccinated participants.. The trial is complete.
Findings
Between Oct 11, 2022, and Jan 9, 2024, 108 participants were enrolled, with 22 assigned to two-dose 106CFU, 26 to two-dose 5 × 105 CFU, 23 to one-dose 106 CFU, and 37 to placebo. 73 participants underwent challenge (16, 18, 13, and 26 participants in the respective groups). Endpoint review committee-adjudicated shigellosis occurred in three (9%) of 34 participants given pooled two-dose vaccine and 21 (81%) of 26 placebo recipients (vaccine efficacy 89% [95% CI 71–96]; p<0·0001). Six participants had grade 3 post-vaccination adverse events, prompting two DSMB reviews; after the first review, the protocol was amended to reduce the vaccine dose and revise eligibility criteria. There was no change after the second review. No vaccine-related serious adverse events or deaths occurred.
Interpretation
In adults in the USA, WRSs2 provided high-level protection against S sonnei shigellosis. Although protection was substantial, the occurrence of a few self-limiting grade 3 adverse events indicates that further optimisation is needed to better define the safety–efficacy balance. These findings support further clinical development of live-attenuated shigella vaccines.
NPR article – A new vaccine could vanquish a major cause of deadly diarrheal disease (Open access)
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