Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells

Nat Med. 2009 Mar;15(3):267-76. doi: 10.1038/nm.1928. Epub 2009 Mar 1.


The variable efficacy of Bacille Calmette Guerin (BCG) vaccination against tuberculosis has prompted efforts to improve the vaccine. In this study, we used autophagy to enhance vaccine efficacy against tuberculosis in a mouse model. We examined the effect of autophagy on the processing of the immunodominant mycobacterial antigen Ag85B by antigen presenting cells (APCs), macrophages and dendritic cells (DCs). We found that rapamycin-induced autophagy enhanced Ag85B presentation by APCs infected with wild-type Mycobacterium tuberculosis H37Rv, H37Rv-derived DeltafbpA attenuated candidate vaccine or BCG. Furthermore, rapamycin enhanced localization of mycobacteria with autophagosomes and lysosomes. Rapamycin-enhanced antigen presentation was attenuated when autophagy was suppressed by 3-methyladenine or by small interfering RNA against beclin-1. Notably, mice immunized with rapamycin-treated DCs infected with either DeltafbpA or BCG showed enhanced T helper type 1-mediated protection when challenged with virulent Mycobacterium tuberculosis. Finally, overexpression of Ag85B in BCG induced autophagy in APCs and enhanced immunogenicity in mice, suggesting that vaccine efficacy can be enhanced by augmenting autophagy-mediated antigen presentation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Autophagy* / drug effects
  • BCG Vaccine / immunology*
  • Dendritic Cells
  • Lysosomes / drug effects
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology
  • Peptides / immunology*
  • Phagosomes / drug effects
  • Phagosomes / immunology
  • Sirolimus / pharmacology


  • BCG Vaccine
  • Peptides
  • Sirolimus