Rapamycin-induced enhancement of vaccine efficacy in mice

Methods Mol Biol. 2012;821:295-303. doi: 10.1007/978-1-61779-430-8_18.

Abstract

Th1 immunity protects against tuberculosis infection in mice and humans. The widely used BCG vaccine primes CD4 and CD8 T cells through signaling mechanisms from dendritic cells and macrophages. The latter express MHC-II and MHC-I molecules through which peptides from BCG vaccine are presented to CD4 and CD8 T cells, respectively. Since BCG sequesters within a phagosome that does not fuse with lysosomes, generation of peptides within antigen-presenting cells infected with BCG occurs with reduced efficiency. We demonstrate that activation of DCs containing BCG vaccine with rapamycin leads to an enhanced ability of DC vaccines to immunize mice against tuberculosis. Coadministration of rapamycin with BCG vaccine also enhanced Th1 immunity. We propose that rapamycin-mediated increase in Th1 responses offers novel models to study mTOR-mediated regulation of immunity.

Publication types

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

MeSH terms

  • Animals
  • BCG Vaccine / administration & dosage
  • BCG Vaccine / immunology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Humans
  • Macrophages / immunology
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology*
  • Phagosomes / immunology
  • Sirolimus / pharmacology*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Tuberculosis / prevention & control*

Substances

  • BCG Vaccine
  • TOR Serine-Threonine Kinases
  • Sirolimus