Oral cholera vaccines have played a critical role in efforts to prevent and control the severe and potentially life-threatening diarrhoeal disease. But experts agree they could be better.
Currently, reports CIDRAP News, the World Health Organisation (WHO) recommends three licensed vaccines for use in areas experiencing cholera outbreaks or where the disease is endemic.
All three are killed, whole-cell vaccines that provide protection against cholera by stimulating the intestinal immune response to the Vibrio cholerae bacterium, which spreads through contaminated water and food and produces toxins that cause severe vomiting, diarrhoea and dehydration.
Clinical trials have found killed oral cholera vaccines have a protective efficacy of around 55%. But they’re less than 30% effective in children under five, who are the most susceptible to dying from cholera.
Plus, they require two doses for maximum efficacy. And with cholera outbreaks increasing in Africa, the global stockpile has been running dry.
“The killed vaccine is a useful tool against cholera, but we don’t have a lot of it, and we need better vaccines,” Andrew Azman, PhD, MHS, an infectious disease epidemiologist with Johns Hopkins Bloomberg School of Public Health, told CIDRAP News.
But results from a phase 1 trial, published this week in The Lancet Infectious Diseases, provide hope that a better vaccine could be on the horizon for a disease that affects up to 4m people a year.
New take on an old idea
The trial, led by a team of scientists and physicians at Mass General Brigham Hospital in Boston, was investigating the safety of PanChol, a single-dose, live-attenuated oral cholera vaccine derived from the V cholerae 01 strain, which has been responsible for most global cholera outbreaks.
The vaccine is the brainchild of Matthew Waldor, MD, PhD, a physician in the infectious diseases department at Mass General Brigham who’s been studying cholera for 30 years.
Waldor said the effort grew out of research he and his colleagues conducted on the cholera strain that raged through Haiti in 2010, which they found was introduced by United Nations Security Forces from Nepal.
“There hadn’t been cholera in Haiti for at least 100 years, and that inspired me to think we need a new vaccine for cholera,” Waldor said. “So we undertook a project to make a live-attenuated vaccine, because there’s good reason to believe a live attenuated vaccine would have single-dose efficacy, especially in children, and that’s who dies from cholera most often.”
Designed to mimic a natural cholera infection, which provides longer-lasting protection against subsequent disease, PanChol (pandemic cholera vaccine) works by colonising the small intestine.
Vaxchora, which is the only cholera vaccine approved for use in the United States, works similarly, but is marketed for people travelling to cholera-endemic areas.
To make the new vaccine safe, Waldor said he and his colleagues introduced 11 genetic mutations to delete the genes for V cholerae toxins and other virulence factors, and included genetic safeguards to ensure that the vaccine strain doesn’t revert and express the cholera toxin again.
But they left the ability of the organism to grow within the small intestine intact.
Waldor said the hope is that the vaccine strain’s replication in the small intestine will offer better immunogenicity than killed oral cholera vaccines and provide “long-lived immunity”.
“We’re taking advantage of the ability of Vibrio cholerae to replicate in our bowel,” said Waldor, who is an inventor on a patent related to PanChol. “That generates more profound immunity.”
The results of the randomised controlled placebo trial, which involved 57 healthy adults in Boston and was designed to assess the safety of PanChol at various dosing levels, showed that the vaccine was well-tolerated at all doses, with no serious adverse events.
The investigators also found that vaccine shedding – a marker for replication – was detectable across vaccine doses. Of note, the results showed that all vaccine recipients developed antibodies that would kill V cholerae.
“Those are a good surrogate for protective immunity,” Waldor said. “So the signals from the study are very promising.”
Azman said he also found the results to be promising. “It’s a new take on an old idea, so it’s likely to work,” he said.
The next step will be to test the vaccine in a cholera-endemic area. To that end, an additional phase 1 trial is scheduled to start this year in Zambia.
Vaccines help, but safe water, sanitation critical
PanChol still has a long way to go, but the development of a single-dose vaccine that provides better protection against cholera could be critical for all areas where the disease is endemic, particularly for African countries, which are experiencing some of the worst cholera outbreaks they’ve seen in decades.
Although cholera is primarily a product of poor sanitation and lack of access to clean water, outbreaks are frequently driven by extreme weather events, conflict, and population displacement.
According to the Africa Centres for Disease Control & Prevention, the continent saw more than 305 903 confirmed and suspected cholera cases in the first half of 2025, and 3 522 deaths. Three countries that have been riven by conflict and natural disasters – Sudan, South Sudan, and the Democratic Republic of the Congo – accounted for more nearly half of those cases.
“When people are displaced, or their regular services are disrupted, that creates conditions that are ripe for cholera,” Azman said.
While Waldor believes a single-dose vaccine for such settings would be a major step forward, ultimately, Azman said, eliminating cholera will require efforts to address the root causes of the disease.
“We focus a lot on vaccines, and sometimes we forget that the bigger picture and the much harder fight is actually providing safe water and sanitation to everyone,” he said.
CIDRAP article – Novel cholera vaccine shows promise in phase 1 trial (Open access)
See more from MedicalBrief archives:
SA starts ground-breaking clinical trials for oral cholera vaccine
Zambia to manufacture cholera vaccine
Desperate countries face world shortage of 50m cholera vaccines