title: A therapeutic anti-Streptococcus mutans monoclonal antibody used in human passive protection trials influences the adaptive immune response.
abstract: The adhesin known as Antigen I/II, P1 or PAc of the cariogenic dental pathogen Streptococcus mutans is a target of protective immunity and candidate vaccine antigen. Previously we demonstrated that immunization of mice with S. mutans complexed with anti-AgI/II monoclonal antibodies (MAbs) resulted in changes in the specificity, isotype and functionality of elicited anti-AgI/II antibodies in the serum of immunized mice compared to administration of bacteria alone. In the current study, an anti-AgI/II MAb reported in the literature to confer unexplained long term protection against S. mutans re-colonization following passive immunization in human clinical trials (MAb Guy's 13), and expressed in tobacco plants (MAb Guy's 13 plantibody), was evaluated for its potential immunomodulatory properties. Immunization of BALB/c mice with immune complexes of Guy's 13 plantibody bound to S. mutans whole cells resulted in a similar change in specificity, isotype, and functionality of elicited anti-AgI/II antibodies as had been observed for other immunomodulatory MAbs. This new information, coupled with the recently solved crystal structure of the adhesin, now provides a rational explanation and plausible mechanism of action of passively administered Guy's 13/Guy's 13 plantibody in human clinical trials, and how long-term prevention of S. mutans carriage well past the application period of the therapeutic antibody could have been achieved.
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32611, USA.
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Robinette
authors.forename: Monika W
authors.initials: MW
authors.lastname: Oli
authors.forename: William P
authors.initials: WP
authors.lastname: McArthur
authors.forename: L Jeannine
authors.initials: LJ
authors.lastname: Brady
mesh_terms: D056704:Adaptive Immunity; D018829:Adhesins, Bacterial / Q000276:immunology* / Q000648:ultrastructure; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines; D003731:Dental Caries / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D013295:Streptococcus mutans / Q000276:immunology*; D014026:Nicotiana / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines