Single-Dose PanChol Shows Strong Safety and Immune Response in Phase 1 trial

A new study published in the journal of The Lancet Infectious Diseases showed that over a 100,000-fold dosage range, a single oral dose of PanChol produced 100% vibriocidal seroconversion and was safe and well tolerated at all tested levels.

Killed whole-cell oral vaccinations are not very effective in young children and need to be administered in many doses. The current 7th pandemic strain of Vibrio cholerae O1 is the source of the single-dose, live-attenuated oral cholera vaccine known as PanChol. It overexpresses the non-toxic cholera toxin B subunit, co-expresses the Inaba and Ogawa antigens, and is engineered to reduce reactogenicity and prevent toxigenic reversion. Thus, this study evaluates PanChol's immunogenicity and safety in a first-in-human experiment.

The participants recruited were healthy people between the ages of 18 and 55 who had never had a cholera infection, had a vaccine, or had a gastrointestinal illness. Participants in the dose-escalation phase were given an extra dosage de-escalation module (10◦–10¹ CFU) in addition to a single oral dose of PanChol ranging from 10¹ to 10¹ CFU.

These participants were randomly assigned (7:7:4) to receive either a placebo or PanChol (2×10¹ or 2×10¹ CFU) during the blinded phase. Safety and vibriocidal seroconversion against Inaba and Ogawa strains at day 15 were co-primary objectives. Stool shedding was one of the secondary results.

57 healthy persons were enrolled between December 13, 2022, and February 7, 2025, where 15 in the dose-escalation module, 6 in the dose-de-escalation module, and 36 in the dose-expansion module (8 getting a placebo, 14 receiving 10¹ CFU PanChol). The majority of participants were White and non-Hispanic, with a median age of 30.6 years and 47% being male.

Everyone got the designated intervention. 38% of placebo receivers and 69% of PanChol recipients had solicited side events, most of which were moderate and temporary. The most frequent occurrence was diarrhea, which was reported at comparable rates in the placebo and vaccination groups. Only 4 incidents exceeded grade 2, and they were all unconnected to vaccination.

Uninvited adverse effects were common but often minor. Nearly all receivers of ≥10¹ CFU PanChol had stool shedding, whereas none received a placebo. Vibriocidal antibodies to both serotypes were seroconverted in all vaccination recipients with ≥10¹ CFU and accessible samples. Overall, PanChol was found to be safe and well-tolerated at all dosages, resulting in 100% vibriocidal seroconversion throughout a 100,000-fold dose range.

Source:

Leitner, D. R., Walsh, S. R., Suzuki, M., Desjardins, M., Hannaford, A., Sherman, A. C., Levine, H., Carr, L., Hammerness, E., Osaki, A., Sullivan, E., Wang, B., Balazs, G. I., Park Chang, J. B., Slater, D. M., Puri, N., Kuehl, C. J., Chen, W. H., Harris, J. B., … PanChol study group. (2026). Safety and immunogenicity of PanChol, a single-dose live-attenuated oral cholera vaccine: results from a phase 1a, double-blind, randomised, placebo-controlled trial. The Lancet Infectious Diseases. https://doi.org/10.1016/S1473-3099(25)00682-6