title: Taking toll: lipid A mimetics as adjuvants and immunomodulators.
abstract: 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.
authors.affiliation: Corixa, Suite 200, 1124 Columbia Street, Seattle, WA 98104, USA. persing@corixa.com
authors.forename: David H
authors.initials: DH
authors.lastname: Persing
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lacy
authors.forename: David A
authors.initials: DA
authors.lastname: Johnson
authors.forename: Jory R
authors.initials: JR
authors.lastname: Baldridge
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hershberg
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: 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
chemical_list: 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