Project Lead(s): Clarence Geyer
Issue
Dental cavities can be prevented by measures such as brushing, flossing and mouthwash.
Despite this, 35% of the global population (2.8 billion people) suffers from tooth decay and cavities in permanent teeth.
In a recent study on the global burden of disease, cavities were the most common of 291 ailments, with the largest increase in cavities occurring in developing countries, highlighting the need for improved dental care.
Solution
The goal of this project was to develop low-cost therapeutic antibodies that block the ability of bacteria to cause dental cavities.
The project team established the methodology to generate antibodies against live bacteria that are important for the formation of dental caries.
Phage display technology was used to screen billions of antibodies against two bacterial strains, Streptococcus mutans (S. mutans) and Streptococcus sobrinius (S. sobrinius) involved in cavity creation.
After observing enrichment in the antibodies binding to S. mutans and S. sobrinius, and after five cycles of the selection protocol, they isolated five antibodies from the phage display selection and determined the sequence of the complementarity determining regions.
The team then measured the interactions of these antibodies against the two bacterial strains and against two negative controls, E. coli and BSA protein, using an ELISA assay. They confirmed interactions of two S. mutans and two S. sobrinus antibodies using immunofluorescence and flow cytometry, consistent with the ELISA results.
Once the antibodies were identified, they were tested in a rat model.
Outcome
The team succeeded in the first stage of the proof of concept by developing novel antibodies that block the ability of bacteria involved in forming dental carries to form biofilm, the initial step required for dental caries.
Promising results were seen when these antibodies were tested in a rat model of dental caries.
Due largely to time constraints, the research team was unable to proceed to the second phase of the proof of concept to express these antibodies in plants and test the ability of the plant material to block formation of dental caries.
The team is continuing to optimize the anti-S. mutans and S.sobrinus antibody design for optimal expression and stability.
They are also working with Prairie Plant Systems in Saskatoon to develop the optimal plant expression system.
After completing this work, they intend to seek transition-to-scale funding, in order to advance the plant-produced products into clinical trials.