LT adjuvant modulates epitope specificity and improves the efficacy of murine antibodies elicited by sublingual vaccination with the N-terminal domain of Streptococcus mutans P1

Milene Tavares Batista, Ewerton Lucena Ferreira, Gisela de Souza Pereira, Phillip Stafford, Denicar Lina Nascimento Fabris Maeda, Juliana Falcão Rodrigues, L. Jeannine Brady, Stephen Johnston, Luís Carlos de Souza Ferreira, Rita de Cássia Café Ferreira

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

In this study, we evaluated the immunogenicity, protective efficacy and peptide-based immune signatures of antibodies raised in mice after sublingual immunization with a recombinant form of the P1 (aka AgI/II, PAc) adhesin (P139-512) of Streptococcus mutans, a major etiological agent of dental caries. Sublingual administration of P139-512 in combination with the mucosal adjuvant LTK4R (a derivative of heat-labile LT toxin) induced strong and long-lasting systemic and mucosal immune responses. Incorporation of the adjuvant resulted in an enhancement of the anti-adhesive and anti-colonization activity against S. mutans as evaluated both under in vitro and in vivo conditions. Incorporation of the adjuvant to the vaccine formulation also changed the epitope specificity of the induced antibodies as determined by immunological signatures of sera collected from vaccinated mice. Use of a peptide microarray library led to the identification of peptide targets recognized by antibodies in serum samples with enhanced anti-adhesive effects. Altogether, the results presented herein showed that the sublingual administration of a P1-based subunit vaccine represents a promising approach for the prevention of dental caries caused by S. mutans. In addition, the present study disclosed the role of adjuvants on the epitope specificity and functionality of antibodies raised by subunit vaccines.

Original languageEnglish (US)
Pages (from-to)7273-7282
Number of pages10
JournalVaccine
Volume35
Issue number52
DOIs
StatePublished - Dec 19 2017

Keywords

  • Anti-caries vaccine
  • Epitope specificity
  • Immunosignature
  • Peptide microarray
  • Streptococcus mutans
  • Sublingual immunization

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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    Batista, M. T., Ferreira, E. L., Pereira, G. D. S., Stafford, P., Maeda, D. L. N. F., Rodrigues, J. F., Brady, L. J., Johnston, S., Ferreira, L. C. D. S., & Ferreira, R. D. C. C. (2017). LT adjuvant modulates epitope specificity and improves the efficacy of murine antibodies elicited by sublingual vaccination with the N-terminal domain of Streptococcus mutans P1. Vaccine, 35(52), 7273-7282. https://doi.org/10.1016/j.vaccine.2017.11.007