This photograph depicts Clostridium difficile colonies after 48 hrs growth on a blood agar plate. Credit: CDC/Dr. Holdeman
Clostridioides difficile (C. diff) causes nearly 500,000 infections annually in the U.S., with approximately 29,000 to 30,000 deaths. A novel vaccination approach that cleared C. diff in an animal model of infection is a major step forward for future vaccine development.
For the study, published in Nature, the researchers administered the experimental vaccine to the mucosal lining of the colon, as clearing the colon is crucial when considering C. diff spore transmission by the fecal-oral route.
“The 30% incidence of recurrent C. diff infection and the documented increase in community-acquired cases among otherwise healthy adults underscore the need for an immunization strategy that prioritizes C. diff clearance,” said D. Borden Lacy, director of the Vanderbilt Center for Structural Biology, and corresponding author of the paper.
The multivalent vaccine combined:
- A selection of novel antigens present on C. diff in both its vegetative state and spore stat,
- Toxins TcdA and TcdB inactivated by point mutations so that they retain native structure,
- An adjuvant to enhance mucosal immune responses.
The researchers compared a rectal route of administration to abdominal cavity injection, and they assessed antibody and cellular immune responses. They found that mucosal immunization cleared C. diff from the host, and that mucosal vaccination protected against illness, death, tissue damage and recurrence. Immune response indicators that correlated with protection and pathogen clearance differed based on the route of vaccine administration.
The researchers also demonstrated that mucosal vaccination provided long-term protection. Animals that were challenged with C. diff infection at 60 and 200 days after the final vaccine dose were protected against illness and death and cleared both vegetative and spore forms of C. diff.
“We expect this strategy to have strong translational value in the effort to develop a human vaccine for C. diff infection, as well as other gut pathogens,” said Lacy.
Data from Vanderbilt University