C.difficile infection (CDI) is a significant public health challenge, causing severe gastrointestinal disease, particularly in healthcare settings and often following antibiotic use. Current management primarily relies on antibiotic treatment and infection control practices; however, this approach is problematic as antibiotics themselves can disrupt the gut microbiome, predisposing individuals to CDI and its recurrence. Furthermore, existing or proposed vaccine strategies often focus on toxins or other bacterial components, which may not provide comprehensive protection or address the full spectrum of disease mechanisms, underscoring a critical need for novel and broadly effective preventative measures against this challenging pathogen.
Our technology utilizes Cwp6 from C.diff, a 675 amino acid surface adhesion protein featuring a signal peptide, N-terminal domain, three cell wall binding repeats, and an amidase_3 catalytic domain. In vivo experiments using mice indicate that when Cwp6 administered with alum adjuvant elicits robust systemic IgG and mucosal IgA antibody responses and confer significant protection against C.diff infection by reducing weight loss, improving survival, decreasing diarrhea, lowering fecal bacterial spores and toxins, and inhibiting bacterial adhesion to human colon epithelial cells. This protein is also conserved across various C.diff ribotypes and toxinotypes, enabling a novel approach different from existing strategies that typically target toxins or other bacterial components.
Immunizations of mice with Cwp6 indicate significant protection against infection with C.diff strain R20291.