Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant

Cell Mol Life Sci. 2008 Oct;65(20):3231-40. doi: 10.1007/s00018-008-8228-6.


The development of non-infectious subunit vaccines greatly increases the safety of prophylactic immunization, but also reinforces the need for a new generation of immunostimulatory adjuvants. Because adverse effects are a paramount concern in prophylactic immunization, few new adjuvants have received approval for use anywhere in the developed world. The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations. Much remains to be learned about this compound's mechanism of action, but recent developments have made clear that it is unlikely to be simply a weak version of lipopolysaccharide. Instead, monophosphoryl lipid A's structure seems to have fortuitously retained several functions needed for stimulation of adaptive immune responses, while shedding those associated with pro-inflammatory side effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Endotoxins / immunology*
  • Humans
  • Lipid A / analogs & derivatives*
  • Lipid A / immunology
  • Lipopolysaccharides / pharmacology
  • Receptors, Immunologic / chemistry
  • Vaccines / immunology*


  • Adjuvants, Immunologic
  • Endotoxins
  • Lipid A
  • Lipopolysaccharides
  • Receptors, Immunologic
  • Vaccines
  • monophosphoryl lipid A