Wednesday, December 4, 2024
12/4/2024
DESCRIPTION (provided by applicant): The mucosal immune system is an important first line of defense against pathogens that cause disease by colonization of or invasion through mucosal tissues, including a variety of childhood diseases such as Dental caries. Nevertheless, little is know about the mucosal immune system in children and their ability to respond with salivary immune responses following mucosal immunization. An initial "window of infectivity" for the oral pathogens mutans streptococci (MS) in infants occurs at 18-24 months of age, a time when primary molar teeth are erupting. It has been proposed that other "windows" open when susceptible teeth erupt, e.g., permanent molar teeth. Therefore, the induction of a salivary antibody response to MS prior to the emergence of a "virgin" tooth may abrogate the colonization of these teeth by MS. The Aims of this application are to determine the ability of preadolescent (age 10-12 years) and preschool (5-6 years of age) children to respond to a recombinant chimeric protein consisting of immunogenic subunits of Agl/ll and glucosyltransferase (SBR-GLU) from S. mutans following mucosal immunization and to determine if the response induced would abrogate the colonization of newly erupted molars by MS. In the first Aim, before beginning studies with SBR-GLU in children, a Phase I Study on adults will be done. Following demonstration of safety and immunogenicity in adults, a 3 x 2 x 2 modified factorial design will compare the effectiveness of the route of immunization and the delivery system in two age groups of children. Serum and saliva will be collected at various times prior to and following immunization and analyzed by ELISA for antibody activity to MS antigens. In a second Aim, saliva and plaque samples from molar teeth will be collected to characterize the establishment of infection with MS on newly erupted molar teeth. Factors such as Dental caries, diet, salivary IgA anti-MS, level of MS in saliva and plaque of erupted teeth will be evaluated for their association with the timing of colonization of newly erupting teeth. The third Aim is to determine the effect of mucosal immunization of children on colonization with MS of virgin tooth surfaces as they erupt (i.e., permanent molar teeth). Saliva, serum and plaque samples will be collected following an immunization that will correspond with the time that permanent molar teeth are erupting, in order to determine if the time to colonization of MS is abrogated as a result of the induced immune response. The information gained regarding the mechanisms involved in the induction of mucosal immune responses in children will be of significant importance in the development of approaches to induce mucosal immunity for the prevention of infectious diseases, including Dental caries and periodontal disease.
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