Taking toll: lipid A mimetics as adjuvants and immunomodulators.
Vaccine adjuvants based on the structure of lipid A, such as monophosphoryl lipid A (MLA), have proven to be safe and effective in inducing immune responses to heterologous proteins in animal and human vaccines. Recent work on the development of a recombinant vaccine for leishmaniasis has demonstrated that a clinical grade MLA formulation - MPL(R) adjuvant - is essential in the development of a protective response. Preliminary evidence suggests that MLA and a chemically distinct family of lipid A mimetics - the aminoalkyl glucosaminide 4-phosphates - act on Toll-like receptor 4 (TLR4). As TLR4 agonists, they have potent immunomodulatory effects when used both as vaccine adjuvants and as stand-alone products. Novel approaches to vaccine development could benefit from taking full advantage of the effects of these compounds on innate and adaptive responses.
Persing
David H
DH
Corixa, Suite 200, 1124 Columbia Street, Seattle, WA 98104, USA. persing@corixa.com
Coler
Rhea N
RN
Lacy
Michael J
MJ
Johnson
David A
DA
Baldridge
Jory R
JR
Hershberg
Robert M
RM
Reed
Steven G
SG
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D029721:Drosophila Proteins; D005260:Female; D007113:Immunity, Innate; D007896:Leishmaniasis / Q000517:prevention & control; D008050:Lipid A / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D008562:Membrane Glycoproteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018716:Molecular Mimicry; D015394:Molecular Structure; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014611:Vaccination
D000276:Adjuvants, Immunologic; D029721:Drosophila Proteins; D008050:Lipid A; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C048436:monophosphoryl lipid A