Immunogenicity and In Vitro and In Vivo Protective Effects of Antibodies Targeting a Recombinant Form of the Streptococcus mutans P1 Surface Protein

Author(s)

Batista, Milene Tavares ^[1] ; Souza, Renata D. ^[1] ; Ferreira, Ewerton L. ^[1] ; Robinette, Rebekah ^[2] ; Crowley, Paula J. ^[2] ; Rodrigues, Juliana F. ^[1] ; Brady, L. Jeannine ^[2] ; Ferreira, Luis C. S. ^[1] ; Ferreira, Rita C. C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Vaccine Dev Lab, Sao Paulo - Brazil

^[2] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 - USA

• Document type: Journal article
• Source: Infection and Immunity; v. 82, n. 12, p. 4978-4988, DEC 2014.
• Web of Science Citations: 7

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. (AU)

• FAPESP's process: 12/51189-3 - Bacillus subtilis as a platform for mucosal vaccines development against human dental caries
• Grantee: Milene Tavares Batista
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/06671-4 - New vaccine antigens for the control of Streptococcus mutans
• Grantee: Rita de Cássia Café Ferreira
• Support Opportunities: Regular Research Grants