Investigating the Effects of IgA Antibodies Elicited by Active Immunization against Clostridiodes difficile on Disease Progression and Severity in Mice

Abstract

Currently, there is no licensed vaccine against Clostridioides difficile. This study explores whether inducing mucosal immune responses (i.e., IgA antibodies), via immunization with C. difficile vaccine candidates may have the potential to prevent infection by promoting clearance of the pathogen in the colonic mucosal compartment. In this study, we evaluate the immune responses elicited in both the mucosal and systemic compartments by a vaccine candidate incorporating a C. difficile cell-surface antigen, PSII, conjugated to CRM197. To elicit a mucosal immune response, mice were immunized via intranasal instillation with PSII:CRM197 formulated with the mucosal adjuvant, CT. To elicit a systemic immune response, mice were immunized intramuscularly with PSII:CRM197 formulated with, AlOH. The study also evaluated immunizing mice with co-administered PSII:CRM197 conjugate and toxin A- (TcdA) and toxin B - (TcdB)- derived toxoids. Primary outcomes were to evaluate antigen-specific IgA responses and determine if IgA levels correlated with C. difficile colonization and disease progression in a C. difficile murine model. Interestingly, the results showed that specific IgA levels against TcdA and TcdB did not correlate with bacterial clearance, however, an increase in anti-TcdB IgA antibodies did correlate with reduced weight loss. For the first time, IgA levels against PSII were detected in sera of immunized mice; however, fecal IgA levels against PSII were still undetected. This does not preclude that there may be an added benefit of including PSII:CRM197 conjugate with the toxoids, and further research is necessary.