A single-dose oral cholera vaccine shows promising results in an early clinical trial

A single-dose oral cholera vaccine shows promising results in an early clinical trial

Clinical trial shows promising results for PanChol, a single-dose oral vaccine that targets up to 4 million cholera cases worldwide each year.

A team of scientists and physicians at Mass General Brigham has developed a single-dose oral cholera vaccine and tested it in a Phase 1 clinical trial. The results were published inThe Lancet Infectious Diseases.

The devastating cholera outbreak in Haiti in 2010 sparked my desire to develop a new oral, live-attenuated cholera vaccine. Existing vaccines made from inactivated bacteria require multiple doses and are not particularly effective, especially in young children, the population most at risk of dying from cholera. Our research into the cholera pathogen has identified opportunities to produce improved vaccines. We hope our vaccine will be used where it is needed most to save lives – in places where cholera is endemic and during outbreaks.”

Matthew K. Waldor, MD, PhD, co-senior author, principal investigator in the Division of Infectious Diseases in the Mass General Brigham Department of Medicine

There are up to 4 million cases of cholera and 143,000 associated deaths each year About 1.3 billion people are at risk of illness caused by its useVibrio choleraeBacteria in contaminated water or food. These bacteria produce toxins that cause severe vomiting and diarrhea.

Waldor and his colleagues derived their new vaccine, called PanChol, from a weakened version of the vaccineVibrio choleraeStrain that is currently responsible for most cholera cases worldwide. The group added certain properties to make the live vaccine safe and prevent it from regaining the ability to produce toxins and cause disease.

In the Phase 1 study involving 57 participants, individuals received escalating doses of PanChol to determine the most effective dose. Based on these findings, additional participants were randomly assigned to either an oral dose of PanChol or an oral dose of placebo.

Because the primary goal of a phase 1 trial is to ensure safety, Waldor and his collaborators were pleased to find that adverse events were typically mild and transient. Whole genome sequencing of PanChol isolated from stool samples of vaccinated participants confirmed the genomic stability of the vaccine, necessary to ensure its safety. Excretion of PanChol, a marker of vaccine replication in the gut, was detectable across all vaccine doses, and 100% of vaccinated people showed strong immune responses to itVibrio choleraeAntigens two weeks after vaccination.

“This work represents a significant advance in our efforts to combat a devastating disease and demonstrates what can be achieved at MGB given the depth of our scientific talent,” said co-senior author Lindsey Baden, MD, vice president for clinical research at Mass General Brigham. “This success is a testament to the collaborative spirit between research scientists and clinical trial experts at Mass General Brigham, who are committed to improving the lives of patients both here and around the world.”

An important next step in PanChol development is to test the vaccine in places where cholera is endemic. To this end, an additional Phase I trial of PanChol will begin in Lusaka, Zambia sometime in early 2026.

Sources: