Summary
In a phase 1a study of 20 healthy adults, 15 developed a fourfold rise in antibody titres against both cholera serotypes after a second PanChol dose. The preprint also reports reduced vaccine shedding after the booster, an indirect measure of intestinal immunity rather than a measure of protection from cholera illness.
A phase 1a study of the oral live-attenuated cholera vaccine PanChol found that 15 of 20 adults (75%) had a fourfold rise in antibody titres against both Vibrio cholerae serotypes tested after receiving a second dose. The medRxiv preprint also reports that 17 participants had no vaccine shedding in stool or only self-limited shedding after the booster, compared with 10% after their first dose.
PanChol is engineered from a current seventh-pandemic El Tor O1 strain and is being developed as a single-dose vaccine. This open-label study examined how immune responses to an initial dose persisted and assessed the safety and immune response to a booster. Its findings are early clinical evidence from a small group of adults; the preprint has not yet been peer reviewed.
What the booster study measured
The 20 participants were healthy adults aged 18–55 who had received one PanChol dose 322–1,111 days earlier. Their initial doses ranged from 10⁵ to 10¹⁰ colony-forming units (CFU). Each received a booster of 2 × 10⁷ CFU. The primary outcome was safety. Secondary measures included vibriocidal antibody titres against the Inaba and Ogawa serotypes and the amount of PanChol detected in stool.
Vibriocidal titres are an immune measure used in cholera research. The study defined seroconversion as a fourfold rise over baseline. Before the booster, titres were already above the level measured before the initial dose in 17 participants for Inaba and 14 for Ogawa. After the booster, 15 participants met the study’s seroconversion definition for both serotypes.
The researchers also compared vaccine shedding after the first dose and booster. Shedding after vaccination was used as a proxy for intestinal mucosal immunity: less shedding after a later dose may indicate that the intestine is less readily colonised by the vaccine strain. After the booster, 17 of 20 participants had no shedding or only self-limited shedding, compared with 10% after the first dose.
Safety findings and the limits of the results
Nine participants (45%) reported at least one solicited adverse event after the booster. Of the 14 reported events, 13 were mild and all were transient. Nausea was the most common, reported by four participants; all cases were mild. Most unsolicited events were also mild. One grade 3 event was judged unrelated to vaccination. Two unsolicited events—a mild gassy sensation and heartburn—were considered related; both occurred on day one and resolved that day.
The antibody and shedding findings provide evidence of immune responses after the booster and are consistent with the authors’ interpretation that the initial dose produced lasting intestinal immunity. The shedding measure is an indirect proxy, however: the study reported safety, antibody titres and vaccine shedding, not cholera illness or protection in a challenge. Whether these signals predict protection from disease will require further clinical development. The study was registered as NCT05657782.