Oral Priming of Mice by Recombinant Spores of Bacillus Subtilis

Vaccine. 2004 Oct 22;22(31-32):4139-43. doi: 10.1016/j.vaccine.2004.05.001.


Recombinant Bacillus subtilis spores were employed as a vaccine delivery system in a heterologous mucosal priming-parenteral boosting vaccination strategy in the mouse model. BALB/c and C57BL/6 mice were orally immunised with recombinant spores expressing tetanus toxin fragment C (TTFC) fused to the spore outer coat protein CotB, and then subcutaneously boosted with soluble TTFC (without adjuvant). Two weeks after boosting, a significantly higher serum TTFC-specific IgG response was stimulated in mice primed with recombinant spores (antibody concentration of 2600 +/- 915 in C57BL/6 and 1200 +/- 370 ng/ml in BALB/c) compared to mice inoculated with wild type spores (650 +/- 250 and 250 +/- 130 ng/ml, respectively). IgG subclass analysis showed a prevalence of IgG1 and IgG2b, indicative of a Th2 type of immune response. Oral administration of recombinant spores stimulated also a significant local TTFC-specific IgA response. These data show that recombinant spores of B. subtilis are able to prime the immune system by the oral route, and that a combined mucosal/parenteral strategy can stimulate both local and systemic antigen-specific immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / analysis
  • Antibodies, Bacterial / biosynthesis
  • Bacillus subtilis / immunology*
  • Bacterial Proteins / immunology
  • Female
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin A / immunology
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Recombinant Proteins / immunology
  • Spores, Bacterial / immunology*
  • Tetanus Toxin / immunology


  • Antibodies, Bacterial
  • Bacterial Proteins
  • CotB protein, Bacillus subtilis
  • Immunoglobulin A
  • Immunoglobulin G
  • Recombinant Proteins
  • Tetanus Toxin