A carbohydrate in the bacterial cell wall of Clostridium difficile has given scientists from the Max Planck Institute a point of attack for a potential vaccine against the pathogen.
Stimulating the immune system – on the basis of a hexasaccharide, scientists have developed a vaccine against C. difficile
Credit Max Planck Institute of Colloids and Interfaces
The sugar-based vaccine has shown a specific and effective immune response in mice, and initial indications are that the substance can stimulate the human immune system to form antibodies against the bacterium.
“Initial testing of the sugar-based antigen synthesised by the team has already produced very promising results,” said Peter N Seeberger, director at the institute.
Chemists developed a synthesis for the essential component of the antigen – a hexasaccharide – which they assembled from four different monosaccharide building blocks. To ensure the monosaccharides bound in the correct place, they blocked other reaction sites. They then conjugated the hexasaccharide to the CRM 197 protein, which is used in many vaccines, as the sugar alone would not elicit an effective immune response.
In order to successfully defend itself against C. difficile, the immune system must also produce another antigen. The chemical glycoprotein conjugate triggered a very effective immune response in two mice that were injected with the substance three times at two-week intervals.
“The fact that the mice are producing antibodies against the carbohydrates is in itself a success,” said Seeberger. “Not all carbohydrates trigger the production of antibodies.”
The antibodies produced by the mice bound exclusively to the sugar – so the antigen cannot cause an autoimmune disease. Additionally, the scientists proved that the antibodies developed against the hexasaccharide are also part of the human immune response.
“We can therefore expect to see that the human immune system produces antibodies against the sugar when vaccinated,” said Seeberger. “Since the natural sugar already elicits the production of a small number of antibodies, we hope that the synthetic glycoprotein conjugate will trigger a more effective response.”
The vaccine will now undergo further testing to see if it can prevents infection in animals – if successful it will be a year or two before it is tested on humans estimates Seeberger.