Pooled analyses of Clostridioides difficile vaccine trials identify baseline predictors for vaccine response

Abstract

Abstract Clostridioides difficile ( C. difficile ) is a major cause of severe diarrhea and colitis usually affecting individuals with dysbiosis. Currently, there is no licensed vaccine nor prophylaxis for C. difficile infection (CDI), while treatment remains challenging. To support immunogenicity assessment and vaccine development programs, we analyzed data from two Sanofi vaccine trials (Phase II and III) with 1,096 participants. We evaluated baseline predictors of 16 seroresponse outcomes, measured 30 days after the third vaccine dose, using five statistical models. Relevant predictors of positive seroresponse after vaccination for both Toxin A and B included lower comorbidity index, age < 65 years, and future CDI risk exposure (i.e., impending hospitalization/nursing facility admission were more relevant than past-exposure history). Higher baseline antibody levels, North American study region, and female sex were mainly related with Toxin B seroresponse. These findings highlight the need for further research to optimize vaccine trial design and personalized vaccination approaches.