Phase 1 durability study of a single dose of the live-attenuated cholera vaccine PanChol and the safety and immunogenicity of a second dose

Background Killed whole-cell oral cholera vaccines require multiple doses and have reduced efficacy in young children, limiting their utility. PanChol is a single-dose, oral live-attenuated cholera vaccine engineered from a current seventh pandemic El Tor O1 Vibrio cholerae strain. PanChol was shown to be safe and immunogenic in a previous phase 1a trial. In participants from this first-in-human trial, we aimed to assess the durability of the initial PanChol dose and the safety and immunogenicity of a second dose. Methods This open-label phase 1a booster study was conducted at Brigham and Women's Hospital (Boston, MA). Eligible participants were healthy adults aged 18-55 years without a history of cholera or gastrointestinal disorders and had received a PanChol dose ranging from 105-1010 colony-forming units (CFU) within the previous 322-1111 days. All participants received a booster dose of 2x107 CFU. The primary outcome was safety, including solicited, unsolicited, and serious adverse events following the second dose of PanChol. Secondary endpoints were the magnitude of pre- and post-vaccination serum vibriocidal titers to both Inaba and Ogawa V. cholerae, including seroconversion (4-fold rise in titers over baseline), and stool shedding of PanChol organisms using quantitative and qualitative stool cultures. Comparisons of the amount of vaccine shedding in stool following primary and secondary immunization were used to assess the intestinal mucosal immunity elicited by the initial PanChol dose. All outcomes were assessed in all participants. This trial is registered with ClinicalTrials.gov, NCT05657782, and is complete. Findings Between Aug 25, 2025, and Feb 20, 2026, 20 healthy adults who previously received a single oral dose of PanChol were enrolled to receive a booster dose of 2x107 CFU. Eleven (55%) of 20 participants were male and the median age was 43{middle dot}6 (IQR 30{middle dot}2-49{middle dot}5). Ten (50%) were White and 17 (85%) were not Hispanic or Latino. Nine (45%) of 20 boost recipients reported at least one solicited adverse event; 13 (93%) of 14 events were mild, and all were transient. The most common solicited adverse event was nausea, reported by 4 (20%) participants; all cases were mild. Most unsolicited adverse events were mild; one was grade 3 and was deemed unrelated to vaccination. Two unsolicited adverse events were deemed related to vaccination (mild gassy sensation and heartburn, both of which occurred on day 1 and resolved the same day). In most participants, vibriocidal antibody titers measured on the day of boosting exceeded baseline titers prior to the initial dose (17 (85%) for Inaba and 14 (70%) for Ogawa). Fifteen (75%) of 20 boost recipients seroconverted vibriocidal antibody titers to both serotypes. After the boost, 17 (85%) participants had no or self-limited vaccine shedding, compared with 10% after the first PanChol dose. Interpretation A second oral dose of PanChol had a favorable safety profile and induced vibriocidal seroconversion to both serotypes in 75% of boost recipients. Intestinal colonization of PanChol following the boost serves as a proxy for measuring mucosal immunity targeting V. cholerae. The decrease in in the abundance of PanChol fecal shedding following the second dose, compared with the first, suggests that a single dose of PanChol is sufficient to confer durable protective immunity against a cholera challenge. These observations underscore the need for further clinical development of PanChol. Funding Wellcome Trust.