FimH as a mucosal adjuvant enhances persistent antibody response and protective efficacy of the anti-caries vaccine

Arch Oral Biol. 2019 May:101:122-129. doi: 10.1016/j.archoralbio.2019.02.009. Epub 2019 Feb 18.

Abstract

Objective: To investigate whether the recombinant FimH-S.T protein could modulate immune response to anti-caries vaccine in vitro and in vivo.

Design: Recombinant FimH protein derived from Salmonella was constructed and purified. The expression of dendritic cell maturation markers and cytokines release were performed by flow cytometry, Real-time PCR and ELISA. In addition, BALB/c mice were administered with anti-caries PAc vaccine plus FimH-S.T, antibody responses were evaluated by ELISA. Splenocytes of immunized mice were detected for their proliferative ability in response to in vitro retreatment with PAc antigen by flow cytometry. Caries protection against dental caries formation was also investigated.

Results: The purified FimH-S.T induced phenotypic maturation of DC2.4 by up-regulating the expression of costimulatory molecules and MHC II, provoked the production and secretion of cytokines via TLR4-dependent signaling pathway in vitro. Furthermore, the mice immunized with the mixture of FimH-S.T and PAc significantly enhanced the PAc-specific antibodies in the serum along with saliva and promoted splenocyte proliferation. Our results also confirmed that PAc+FimH-S.T decreased the caries lesions formation which provided high protective efficacy against dental caries.

Conclusion: Our study demonstrates that recombinant FimH-S.T could enhance specific IgA responses and protection of anti-caries vaccine, possessing mucosal adjuvant ability by activating DC2.4 via TLR4 signaling pathway.

Keywords: Adjuvant; Dental caries; FimH; Mucosal immunity; Salivary immunoglobulin A.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antibodies, Bacterial / immunology
  • Antibody Formation
  • Dental Caries / prevention & control*
  • Fimbriae Proteins / pharmacology*
  • Immunity, Mucosal*
  • Immunoglobulin A / immunology
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / pharmacology
  • Toll-Like Receptor 4 / metabolism
  • Vaccines / therapeutic use*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Immunoglobulin A
  • Recombinant Proteins
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Vaccines
  • Fimbriae Proteins