Oral immunization of humans and experimental animals with Streptococcus mutans antigens induces specific IgA enzyme- neutralizing antibodies which inhibit S. mutans growth, acid production and phosphotransferase (PTS), reduced numbers of plaque-adherent S. mutans and carious lesions suggesting that IgA antibodies inhibit some or all of the essential steps in S. mutans- induced cariogenicity such as adherence, glucan synthesis, production of lactate or other enzyme activities. The functional aspects of naturally occurring human salivary and colostral IgA1 and IgA2 and serum IgG, IgA and IgM antibodies and their interaction with the innate factors, lactoferrin, lysozyme and peroxidase in inhibiting virulence factors of S. mutans which are important in dental caries formation will be the major focus of this proposal. The levels, specificities and isotypes of parotid salivary and serum antibodies from caries-resistant (CR) and caries-susceptible (CS) subjects to S. mutans antigens will continue to be determined using an ELISA. IgA subclass antigenic specificity will be determined. IgA, IgG and IgM from immunized animals, CR and CS subjects and colostrum will be purified by affinity chromatography and used to treat S. mutans cells and purified enzymes to determine if the purified antibodies will inhibit S. mutans growth, adherence to glass surfaces, acid production, glucan synthesis and glucosyltransferase, fructosyltransferase, lactate dehydrogenase, PTS, dextranase and invertase activities. Kinetics of these enzyme activities will be examined. IgA will be subjected to jacalin chromatography and FPLC to isolate polymeric and monomeric IgA1 and IgA2 and will be used in our neutralization studies. Differences in avidity of CR and CS IgA1 and IgA2 antibody fractions will be studied. The differential effects of IgA1 and IgA2 from CR and CS subjects will be investigated by mixing the fractions and using them in the inhibition assays. Lactoferrin, lysozyme, peroxidase, fluoride and chlorhexidine will be added to the fractionated CR and CS IgA1 and IgA2 and used in our neutralization assays. The purified IgA1 and IgA2 from the CR and CS subjects and normal neutrophils will be examined for their ability to opsonize, phagocytize and kill S. mutans. The role of S. mutans fimbriae will be investigated as a potential vehicle for the adherence of the organism. These studies should provide valuable information on the actual function of IgA1 and IgA2 antibodies important in caries protection and the nature of the S. mutans antigen(s) most relevant in inducing protective immunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE007318-04
Application #
3220915
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1984-12-01
Project End
1991-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322