Development of Anti-Dental Caries Vaccine Using Recombinant Lactic Streptococci

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Streptococcus mutans has been implicated as a causative organism of human dental caries. S. Mutans produces a cell surface protein antigen (PAc) with a molecular mass of 190 kilodaltons. In this study, we constructed a recombinant lactic streptococcus with carries th pac gene of S. Mutans for development of an oral vaccine against dental caries.1. We cloned the pac gene of S. Mutans MT8148 (serotype c) and determined the complete nucleotide sequence of the gene. The pac gene consisted of 4,695 base pairs. The initial gene product contained 1,565 amino acids and had a molecular weight of 170,773.2. To make clear the biological function of PAc, we constructed genetically several PAc-defective transformants fo S. mutans. The cell hydrophobicity of PAc-defective transformants was markedly lower than that of the parent strain. Resting cells of the hydrophilic strains attached in lower number to saliva-coated hydroxyapatite than did the parent strain. These findings suggest that cell surface PAc of S. Mutans participates in attachment of the streptococcal cell to aquired pellicles on tooth surfaces.3. Homology between PAc of S. Mutans and a 210-kilodalton protein antigen of Streptococcus sobrinus was high in the central regions.4. The pac gene from S. mutans was joined to shuttle vector pSA3. The chimeric plasmid pSM1 was successfully transformed into Streptococcus lactis. The recombinant S. Lactis produced a small amount of PAc. Significant salivary immunoglobulin A and serum immunoglobulin G responses to PAc were induced in mice immunized orally with the recombinant S. lactis.