This Small Business Innovation Research grant application is based on the report that certain monoclonal antibodies that recognize a 185kDa surface protein antigen present on the cariogenic bacterium, Streptococcus mutants, when applied to human teeth, after thorough professional cleaning and chlorhexidine treatment, prevent recolonization of the mouth by S. mutants for prolonged periods. Previous studies in rhesus monkeys showed that this treatment prevented the emergence of S. mutants in the oral microbiota and the development of dental caries when the monkeys were maintained on a high sucrose diet. As the cost involved in the production of monoclonal antibodies by current technologies is prohibitively high, development of such topical antibody treatments for caries prevention will require radically different approaches to antibody production. This application proposes to generate such antibodies ultimately in edible plant material that would not only produce the large amounts envisaged but also substantially reduce or even eliminate much of the expensive processing required to yield a practical product. Initially in Phase I it is proposed to construct vectors containing (separately) heavy and light chain immunoglobulin genes with variable regions representing the known sequence of a mouse monoclonal antibody (Guy's 13) to the 185kDa protein suitable for expression in tobacco plants (Specific Aim 1).
In Specific Aim 2, expression of the recombinant antibodies will be tested in protoplast tissue culture, as a quicker procedure than growing plants by conventional means. In Phase II, it is proposed to express these """"""""plantibodies"""""""" in alfalfa, and to test the ability of this material to reduce colonization of S. mutants in a rat model of dental caries.
| Weintraub, J A; Hilton, J F; White, J M et al. (2005) Clinical trial of a plant-derived antibody on recolonization of mutans streptococci. Caries Res 39:241-50 |
