Novel generation mycobacterial adjuvant based on liposome-encapsulated monomycoloyl glycerol from Mycobacterium bovis bacillus Calmette-Guérin

J Immunol. 2009 Aug 15;183(4):2294-302. doi: 10.4049/jimmunol.0804091. Epub 2009 Jul 20.


The immunostimulatory activity of lipids associated with the mycobacterial cell wall has been recognized for several decades and exploited in a large variety of different adjuvant preparations. Previously, we have shown that a mycobacterial lipid extract from Mycobacterium bovis bacillus Calmette-Guérin delivered in cationic liposomes was a particular efficient Th1-inducing adjuvant formulation effective against tuberculosis. Herein, we have dissected the adjuvant activity of the bacillus Calmette-Guérin lipid extract showing that the majority of the activity was attributable to the apolar lipids and more specifically to a single lipid, monomycoloyl glycerol (MMG), previously also shown to stimulate human dendritic cells. Delivered in cationic liposomes, MMG induced the most prominent Th1-biased immune response that provided significant protection against tuberculosis. Importantly, a simple synthetic analog of MMG, based on a 32 carbon mycolic acid, was found to give rise to comparable high Th1-biased responses with a major representation of polyfunctional CD4 T cells coexpressing IFN-gamma, TNF-alpha, and IL-2. Furthermore, comparable activity was shown by an even simpler monoacyl glycerol analog, based on octadecanoic acid. The use of these synthetic analogs of MMG represents a promising new strategy for exploiting the immunostimulatory activity and adjuvant potential of components from the mycobacterial cell wall without the associated toxicity issues observed with complex mycobacterial preparations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • BCG Vaccine / administration & dosage*
  • BCG Vaccine / immunology*
  • Cells, Cultured
  • Female
  • Glycerol / administration & dosage
  • Glycerol / immunology
  • Liposomes / administration & dosage
  • Liposomes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Monoglycerides / administration & dosage*
  • Monoglycerides / immunology*
  • Mycobacterium bovis / immunology*
  • Mycolic Acids / administration & dosage
  • Mycolic Acids / immunology


  • Adjuvants, Immunologic
  • BCG Vaccine
  • Liposomes
  • Monoglycerides
  • Mycolic Acids
  • monomycoloyl glycerol
  • Glycerol