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Endotoxins: Structure, Function and Recognition pp 303–321Cite as

Synthetic and Natural TLR4 Agonists as Safe and Effective Vaccine Adjuvants

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Part of the book series: Subcellular Biochemistry ((SCBI,volume 53))

Abstract

Natural derivatives and synthetic analogues of lipopolysaccharide are potent stimulators of the mammalian immune system. Retained adjuvant activity with reduced toxicity was obtained by the development of monophosphoryl lipid A (MPL®), which is approved for use in several vaccine products. Ongoing research and development of synthetic TLR4 agonists may offer increased purity and biological activity with reduced cost. Extensive research has elucidated the mechanism of action of TLR4 agonists and structure-function relationships. Moreover, the formulation of TLR4 agonists has been shown to significantly affect the type and magnitude of elicited immune response. TLR4 agonists comprise a promising class of adjuvants for safe and effective vaccines.

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Abbreviations

AGP:

aminoalkyl glusosaminide 4-phosphate

CTL:

cytotoxic T lymphocyte

DLPC:

1,2-dilauroyl-sn-glycero-3-phosphocholine

DMPC:

1,2-dimyristoyl-sn-glycero-3-phosphocholine

DPPC:

1,2-dipalmitoyl-sn-glycero-3-phosphocholine

DPPG:

1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol)

DPTAP:

1,2-dipalmitoyl-3-trimethylammonium-propane

DSC:

differential scanning calorimetry

FTIR:

Fourier-transform infrared spectroscopy

GLA:

glucopyranosyl lipid A

GLA-SE:

stable emulsion containing glucopyranosyl lipid adjuvant

HPV:

human papilloma virus

ITC:

isothermal titration calorimetry

LBP:

lipopolysaccharide-binding protein

LPS:

lipopolysaccharide

LRR:

leucine-rich repeat

Mal:

MyD88-adapter-like

MAPK:

mitogen-activated protein kinase

MPL:

monophosphoryl lipid A

MPL-AF:

aqueous formulation of monophosphoryl lipid A

MPL-SE:

stable emulsion containing monophosphoryl lipid A

MyD88:

myeloid differentiation primary response gene (88)

NF-κβ:

nuclear factor-κβ

PAMP:

pathogen-associated molecular pattern

PRR:

pattern-recognition receptor

TLR:

Toll-like receptor

TNF-α:

tumor necrosis factor-α

TRIF:

TIR-domain-containing adapter-inducing interferon-β

TRAM:

TRIF-related adapter molecule

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Authors and Affiliations

  1. Infectious Disease Research Institute, 1124 Columbia St, Ste 400, Seattle, WA, 98104, USA

    Christopher B. Fox, Steven G. Reed & Gregory C. Ireton

  2. World Health Organization, Initiative for Vaccine Research, 20 Avenue Appia, CH-12211, Geneva 27, Switzerland

    Martin Friede

Authors
  1. Christopher B. Fox
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  2. Martin Friede
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  3. Steven G. Reed
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  4. Gregory C. Ireton
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Correspondence to Gregory C. Ireton .

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  1. Dept. Biochemistry, Jiangnan University, Wuxi, Jiangsu, 214122, China, People's Republic

    Xiaoyuan Wang

  2. European Southern Observatory (ESO), Karl-Schwarzschild-Str. 2, Garching, 85748, Germany

    Peter J. Quinn

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Fox, C.B., Friede, M., Reed, S.G., Ireton, G.C. (2010). Synthetic and Natural TLR4 Agonists as Safe and Effective Vaccine Adjuvants. In: Wang, X., Quinn, P. (eds) Endotoxins: Structure, Function and Recognition. Subcellular Biochemistry, vol 53. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9078-2_14

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