Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant.
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.
Casella
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Institute for Cellular Therapeutics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
Mitchell
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D004731:Endotoxins / Q000276:immunology*; D006801:Humans; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000737:chemistry; D014612:Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D014612:Vaccines; C048436:monophosphoryl lipid A