Advantages:
- Enhanced Vaccine Conservation: This technology ensures the conservation of critical vaccine components across diverse C. difficile strains, improving vaccine effectiveness.
- Immunogenic Potential: RBD2, a key discovery, exhibits exceptional immunogenicity, promising robust immune responses in vaccine recipients.
- Inhibition of CDT Activity: Anti-RBD2 and anti-RBD1+2 serum have demonstrated the ability to inhibit CDT-mediated cell rounding, highlighting their potential in preventing C. difficile infections.
Summary:
Clostridioides difficile (C. difficile) is a spore-forming and toxin-producing anaerobic bacterium that causes antibiotic-associated diarrhea and life-threatening colitis. Currently, treatment options of C. difficile infection (CDI) are a few antibiotics that are plagued by high recurrence rates (15-35%) and increasing resistance. There is currently no vaccine that can prevent CDI and recurrence.
Our researchers investigated the third C. difficile toxin termed binary toxin (CDT), which in addition to the two exotoxins TcdA and TcdB is responsible for the main symptoms of CDI. CDT is composed of the enzymatic CDTa and the translocation component CDTb. The researchers analyzed the cytotoxic effect of CDTa/CDTb and evaluated the immunogenicity of RBD1 and RBD2 (the two receptor binding domains of CDTb). The research demonstrates the remarkable immunogenicity of RBD2, positioning it as a promising candidate. Upon administration, RBD2 elicits significant antibody responses and offers protection against CDT challenges, setting it apart from RBD1. Furthermore, the study showcases the potential of anti-RBD2 and anti-RBD1+2 serum to inhibit CDT-mediated cell rounding, reaffirming the significance of RBD2 in vaccine development against CDI. In summary, this research underscores RBD2's immunogenic potential, paving the way for the development of innovative vaccines to combat this prevalent and challenging infection.
Fig 1: A) RBD2 or RBD1+2 immunization, but not RBD1 immunization, protects mice against lethal CDT challenge. B) Cleaved CDTb (mTcdB) alone is not toxic to mice, as observed after immunization with RBD1, RBD2, or RBD1+2.
Desired Partnerships:
- License
- Sponsored Research
- Co-Development