Mass General Brigham–Developed Cholera Vaccine Completes Phase 1 Trial

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, with results published in The Lancet Infectious Diseases.

“The devastating cholera outbreak in Haiti in 2010 triggered my desire to create a new oral live-attenuated cholera vaccine,” said co-senior author Matthew K. Waldor, MD, PhD, a principal investigator in the Division of Infectious Diseases in the Mass General Brigham Department of Medicine. “Existing vaccines made from inactivated bacteria require multiple doses and are not that efficacious, particularly in young children, the population most at risk of dying from cholera. Our research on the cholera pathogen suggested ways to make improved vaccines. We hope our vaccine will be deployed where it is most needed to save lives—in places where cholera is endemic and during outbreaks.”

Up to 4 million cholera cases and 143,000 related deaths occur annually, with approximately 1.3 billion people at risk of disease, which is caused by ingestion of Vibrio cholerae bacteria in tainted 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 Vibrio cholerae strain that is currently responsible for most global cholera cases. The group added certain characteristics to make the live vaccine safe and prevent it from regaining the ability to produce toxins and cause disease.

 In the 57-participant phase 1 trial, individuals received increasing doses of PanChol to identify the most effective dose. Based on these findings, additional participants were randomly assigned to receive either one oral dose of PanChol or one oral dose of placebo.

As the most important goal of a phase 1 trial is to ensure safety, Waldor and his collaborators were pleased to observe that adverse events were typically mild and transient. Whole-genome sequencing of PanChol isolated from vaccinated participants’ stool samples confirmed the vaccine’s genomic stability, which is needed to ensure its safety. PanChol shedding, a marker for vaccine replication in the intestine, was detectable across vaccine doses, and 100% of people who were vaccinated mounted strong immune responses against Vibrio cholerae antigens two weeks after vaccination.

"This work represents a significant step forward in our efforts to combat a devastating disease and shows what can be accomplished at MGB given the depth of our scientific talent,” said co-senior author Lindsey Baden, MD, vice president of clinical research at Mass General Brigham. “This achievement is a testament to the collaborative spirit among research scientists and clinical trial experts at Mass General Brigham who share a commitment to improving the lives of patients both here and globally.”

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