Immunogenicity and in vitro and in vivo protective effects of antibodies targeting a recombinant form of the Streptococcus mutans P1 surface protein

Milene Tavares Batista, Renata D. Souza, Ewerton L. Ferreira, Rebekah Robinette, Paula J. Crowley, Juliana F. Rodrigues, L. Jeannine Brady, Luís C.S. Ferreira, Rita C.C. Ferreira

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 (P139-512), 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 P139-512 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 P139-512 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, P139-512-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- P139-512 antibodies, particularly those raised in combination with adjuvants. In conclusion, our results confirm the utility of P139-512 as a potential candidate for the development of anticaries vaccines and as a tool for functional studies of S. mutans P1.

Original languageEnglish (US)
Pages (from-to)4978-4988
Number of pages11
JournalInfection and immunity
Volume82
Issue number12
DOIs
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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