Researchers from the University of Exeter in collaboration with a team at Paris-SUD University have made a breakthrough in the hunt for a new vaccine for killer hospital bug Clostridioides difficile (C. diff). The University of Exeter investigators first identified a gene in C. diff responsible for producing a protein that aids in binding the bacteria to the gut of its victims. Then in collaboration with the Paris-SUD University team they showcased how mice vaccinated with this protein generated specific antibodies to the protein—and that C diff. did not produce this protein and was less able to attach to the gut.
One study in 2015 revealed that C diff caused nearly 500,000 infections in the United States leading to 15,000 deaths. Although there are several C. diff toxin-targeted vaccines in clinical trials, in 2017 Sanofi scrapped its efforts to find a toxin-based C. diff vaccine after many years citing too low a probability of success.
Research Background and Players: GW4 Alliance
This research initially commenced as a collaborative between the University of Exeter, Novartis and the University of Nottingham. Thereafter, it evolved to also include the University of Bath and University Paris-Sud. Both the University of Bath and Exeter are part of the GW4 Alliance, a collaborative research alliance of research-intensive and innovative universities in the South West of UK and Wales.
The C. diff bacteria must bind to the gut to produce the toxin that causes illness. The Exeter and Paris-SUD University team are hopeful that vaccination against attachment will be effective in humans as the preclinical study was with mice.
No C. diff Vaccine
Currently there is no C. diff vaccine in widespread use. There are some toxin-based vaccines in clinical trials, but the Exeter research reveals a promising alternative.
The team identified the gene called CDO873—one that generates a protein that helps C. diff bind to the gut. The researchers noted, “This binding is thought to be key for C. diff infections, so if we can present adhesion of bacteria then there’s a real possibility of preventing the disease.” The researchers also immunized the mice with the CDO873 protein in isolation (not as part of a C. diff bacterium) and found a “strong” immune response. The group at University Paris-Sud conducted ongoing experiments revealing that mice develop antibodies when immunized with the CDO873 protein while the Bath researchers were able to map the 3D molecular structure of CDO873 at high resolution using the high-brightness X-ray beam at the UK’s state-of-the-art facility, Diamond Light Source at Didcot in Oxfordshire offering more information on its function.
The study was published in the Journal of Biological Chemistry and is titled “Molecular features of lipoprotein CDO873: A potential vaccine against the human pathogen Clostridioides difficile.”
WJ Bradshaw, University of Bath
JF Bruxelle, University Paris-Sud
A Kovacs-Simon, University of Exeter
NJ Harmer, University of Exeter
C. Janoir, University Paris-Sud
S Pechine, University Paris-Sud
KR Acharya, University of Bath
SL Michell, University of Exeter
Call to Action: Interested in this preclinical research probing the C. diff vaccine—connect with the authors and the GW4 Alliance.