Bacillus Subtilis Spores: A Novel Microparticle Adjuvant Which Can Instruct a Balanced Th1 and Th2 Immune Response to Specific Antigen

Eur J Immunol. 2007 Jun;37(6):1538-47. doi: 10.1002/eji.200636875.


There is a current need for safe, cheap, and effective vaccine adjuvants, to combine with sub-unit antigens to enhance their immunogenicity. In this study we have used probiotic Bacillus subtilis spores, known to be safe and fully tolerated by ingestion in man, and explored their ability to influence the magnitude and diversity of immune responses induced against two model antigens, tetanus toxoid fragment C (TT) and ovalbumin (OVA) in mice. The results show that B. subtilis spores not only increased antibody and T cell responses to a co-administered soluble antigen, but also broadened them, to include both antigen-specific CD4+ and CD8+ T cell responses as well as complement and non-complement fixing antibody isotypes. Furthermore, following intranasal immunization, spores augmented specific IgA to co-administered antigen both in the local respiratory and distal vaginal mucosa, as well as increased antigen-specific IgG antibody in draining LN and blood. Collectively, these data demonstrate that naturally occurring, non-pathogenic, non-commensal spores of B. subtilis both instruct and augment polyvalent immune responses and highlight their clinical potential in future vaccines to generate broad-based immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Administration, Intranasal
  • Animals
  • Bacillus subtilis / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cervix Uteri / chemistry
  • Cervix Uteri / immunology
  • Cytokines / metabolism
  • Egg Proteins / immunology
  • Female
  • Immunity, Mucosal / immunology
  • Immunoglobulin A / analysis
  • Immunoglobulin A / blood
  • Immunoglobulin G / analysis
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Ovalbumin / immunology
  • Peptide Fragments
  • Spleen / cytology
  • Spleen / immunology
  • Spores, Bacterial / immunology*
  • Tetanus Toxoid / chemistry
  • Tetanus Toxoid / immunology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Vaccination
  • Vagina / chemistry
  • Vagina / immunology


  • Adjuvants, Immunologic
  • Cytokines
  • Egg Proteins
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • OVA-8
  • Peptide Fragments
  • Tetanus Toxoid
  • Ovalbumin