Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant |
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Authors: | C R Casella T C Mitchell |
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Institution: | (1) Institute for Cellular Therapeutics, University of Louisville School of Medicine, Louisville, KY 40202, USA;(2) Dept. of Microbiology and Immunology, University of Louisville School of Medicine, 570 S. Preston St., Donald Baxter Bldg., 4th floor, Louisville, KY 40202, USA |
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Abstract: | 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.
Received 25 April 2008; received after revision 05 June 2008; accepted 10 June 2008 |
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Keywords: | " target="_blank"> Endotoxin monophosphoryl lipid A vaccine adjuvant immunity inflammatory toxicity MD-2 Tolllike receptor 4 |
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