Citation

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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

Winter, K;Houle, S;Dozois, CM;Ward, BJ;

Clostridioides difficile remains a major public health threat, and new approaches are needed to develop an effective vaccine. To date, the industry has focused on intramuscular vaccination targeting the C. difficile toxins. Multiple disappointing results in phase III trials have largely confirmed that this may not be the best strategy. As C. difficile is a pathogen that remains in the intestine, we believe that targeting mucosal immune responses in the gut will be a more successful strategy. We have repurposed a highly attenuated Salmonella 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.