Multimodal vaccination targeting the receptor binding domains of Clostridioides difficile toxins A and B with an attenuated Salmonella Typhimurium vector (YS1646) protects mice from lethal challenge.

Typhimurium (YS1646), originally pursued as a cancer therapeutic, as a vaccine vector. Using a multimodal vaccination strategy (both recombinant protein delivered intramuscularly and YS1646 expressing antigen delivered orally), we elicited both systemic and local immune responses. Oral vaccination alone completely protected mice from lethal challenge. Given the established safety profile of YS1646, we hope to move these vaccine candidates forward into a phase I clinical trial.