Redirecting the humoral immune response against Streptococcus mutans antigen P1 with monoclonal antibodies.
The adhesin P1 of Streptococcus mutans has been studied as an anticaries vaccine antigen. An anti-P1 monoclonal antibody (MAb) bound to S. mutans prior to mucosal immunization of mice was shown previously to alter the amount, specificity, isotype, and biological activity of anti-P1 antibodies. The present study was undertaken to screen this and four additional anti-P1 MAbs for immunomodulatory activity when complexed with S. mutans and administered by a systemic route and to evaluate sera from immunized mice for the ability to inhibit adherence of S. mutans to immobilized human salivary agglutinin. All five MAbs tested influenced murine anti-P1 serum antibody responses in terms of subclass distribution and/or specificity. The effects varied depending on which MAb was used and its coating concentration. Two MAbs promoted a more effective, and two others a less effective, adherence inhibition response. An inverse relationship was observed between the ability of the MAbs themselves to inhibit adherence and the ability of antibodies elicited following immunization with immune complexes to inhibit adherence. Statistically significant correlations were demonstrated between the levels of anti-P1 serum immunoglobulin G2a (IgG2a) and IgG2b, but not of IgG1 or IgG3, and the ability of sera from immunized animals to inhibit bacterial adherence. These results indicate that multiple anti-P1 MAbs can mediate changes in the immune response and that certain alterations are potentially more biologically relevant than others. Immunomodulation by anti-P1 MAbs represents a useful strategy to improve the beneficial immune response against S. mutans.
Oli
Monika W
MW
Department of Oral Biology, P.O. Box 100424, Health Science Center, University of Florida, Gainesville, FL 32610-0424, USA.
Rhodin
Nikki
N
McArthur
William P
WP
Brady
L Jeannine
LJ
D018829:Adhesins, Bacterial / Q000276:immunology*; D000373:Agglutinins / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001422:Bacterial Adhesion; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D051379:Mice; D008807:Mice, Inbred BALB C; D012463:Saliva / Q000276:immunology; D013295:Streptococcus mutans / Q000276:immunology*
D018829:Adhesins, Bacterial; D000373:Agglutinins; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G