Despite considerable knowledge of dental caries pathogenesis, this transmissible infectious disease is still a worldwide public health problem, affecting mainly populations under high Streptococcus mutans challenge. Although use of fluoride has beneficial effect, poor oral hygiene and high sucrose consumption continue to promote early S. mutans infection and disease. Preclinical studies with dental caries vaccines have successfully interfered with S. mutans infection and disease. This approach requires a level of secretory immune maturity sufficient for adequate response to virulence antigen(s) contained within these vaccines before infection. Children normally challenged with S. mutans become infected between 18-36 months of age and form salivary IgA antibody to several S. mutans antigens. However, poorly understood are secretory immune responses to these antigens in children who become colonized much earlier due to heavy challenge. To this end, the NIDCR has requested studies of the relationships of adaptive immunity to S. mutans, degree of infection, and caries development. We propose a prospective study to investigate IgA antibody responses to initial colonizers (S. mitis) and pathogenic bacteria (S. mutans) during the period of initial oral establishment of S. mutans in a population undergoing heavy S. mutans infectious challenge. 160 children will be followed at 6m intervals from 6-12m until 24-30m of age. Clinical examinations will be followed by microbiological exams at each interval to analyze levels of infection by S. mitis and S. mutans. The genetic diversity and stability of S. mutans clones will be measured. Salivary samples will be collected to measure total levels of IgA and levels of IgA antibody to S. mitis/S. mutans secreted/surface-associated antigens. Patterns and extent of IgA responses to these streptococcal strains will be compared to assess relative maturation of secretory immune responses. These data will then be analyzed with respect to the time and intensity of S. mutans infection and development of dental caries. These studies should help to define vaccine approaches targeting children at high risk for dental caries.
