title: Immunogenicity and in vitro and in vivo protective effects of antibodies targeting a recombinant form of the Streptococcus mutans P1 surface protein.
abstract: Streptococcus mutans is a major etiologic agent of dental caries, a prevalent worldwide infectious disease and a serious public health concern. The surface-localized S. mutans P1 adhesin contributes to tooth colonization and caries formation. P1 is a large (185-kDa) and complex multidomain protein considered a promising target antigen for anticaries vaccines. Previous observations showed that a recombinant P1 fragment (P1(39-512)), produced in Bacillus subtilis and encompassing a functional domain, induces antibodies that recognize the native protein and interfere with S. mutans adhesion in vitro. In the present study, we further investigated the immunological features of P1(39-512) in combination with the following different adjuvants after parenteral administration to mice: alum, a derivative of the heat-labile toxin (LT), and the phase 1 flagellin of S. Typhimurium LT2 (FliCi). Our results demonstrated that recombinant P1(39-512) preserves relevant conformational epitopes as well as salivary agglutinin (SAG)-binding activity. Coadministration of adjuvants enhanced anti-P1 serum antibody responses and affected both epitope specificity and immunoglobulin subclass switching. Importantly, P1(39-512)-specific antibodies raised in mice immunized with adjuvants showed significantly increased inhibition of S. mutans adhesion to SAG, with less of an effect on SAG-mediated bacterial aggregation, an innate defense mechanism. Oral colonization of mice by S. mutans was impaired in the presence of anti-P1(39-512) antibodies, particularly those raised in combination with adjuvants. In conclusion, our results confirm the utility of P1(39-512) as a potential candidate for the development of anticaries vaccines and as a tool for functional studies of S. mutans P1.
authors.affiliation: Vaccine Development Laboratory, Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Milene Tavares
authors.initials: MT
authors.lastname: Batista
authors.affiliation: Vaccine Development Laboratory, Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Renata D
authors.initials: RD
authors.lastname: Souza
authors.affiliation: Vaccine Development Laboratory, Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Ewerton L
authors.initials: EL
authors.lastname: Ferreira
authors.affiliation: Department of Oral Biology, University of Florida, College of Dentistry, Gainesville, Florida, USA.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Robinette
authors.affiliation: Department of Oral Biology, University of Florida, College of Dentistry, Gainesville, Florida, USA.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Crowley
authors.affiliation: Vaccine Development Laboratory, Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Juliana F
authors.initials: JF
authors.lastname: Rodrigues
authors.affiliation: Department of Oral Biology, University of Florida, College of Dentistry, Gainesville, Florida, USA.
authors.forename: L Jeannine
authors.initials: LJ
authors.lastname: Brady
authors.affiliation: Vaccine Development Laboratory, Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Luís C S
authors.initials: LC
authors.lastname: Ferreira
authors.affiliation: Vaccine Development Laboratory, Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil ritacafe@usp.br.
authors.forename: Rita C C
authors.initials: RC
authors.lastname: Ferreira
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000373:Agglutinins / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D001412:Bacillus subtilis / Q000235:genetics; D001422:Bacterial Adhesion; D003731:Dental Caries / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009055:Mouth / Q000382:microbiology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012463:Saliva / Q000378:metabolism; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013295:Streptococcus mutans / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000373:Agglutinins; D000907:Antibodies, Bacterial; D008565:Membrane Proteins; D011994:Recombinant Proteins; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic