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Chemically Synthesized TLR4 Ligands, Their Immunological Functions, and Potential as Vaccine Adjuvant

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The Role of Toll-Like Receptor 4 in Infectious and Non Infectious Inflammation

Part of the book series: Progress in Inflammation Research ((PIR,volume 87))

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Abstract

Lipopolysaccharide (LPS), the major glycoconjugates in the outer membrane of Gram-negative bacteria, and its active center glycolipid, lipid A, are recognized by an innate immune system receptor, Toll-like receptor (TLR) 4, and trigger immunostimulatory effects and thus have the potential to act as vaccine adjuvants. Although canonical Escherichia coli LPS induces strong inflammation and acts as an endotoxin due to the ability that hyperstimulates the immune system, recent studies revealed that inflammatory activity of lipid A can be attenuated by the structural modification. Here, we discuss the structure–activity relationship of lipid A and the potential as a vaccine adjuvant, and introduce currently used vaccines that contain LPS and lipid A. We also introduce the strategy of safe lipid A adjuvant development based on human symbiotic bacterial lipid As. Finally, we present studies on lipid A–based self-adjuvant strategy and how structural modifications and conjugations can help regulate the adjuvanticity of lipid A.

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  1. Osaka University, Toyonaka, Osaka, Japan

    Atsushi Shimoyama & Koichi Fukase

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  1. Atsushi Shimoyama
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  2. Koichi Fukase
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Correspondence to Koichi Fukase .

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Editors and Affiliations

  1. Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Carlo Rossetti

  2. Department of Biotechnology and Biosciences, University of Milano Bicocca, Milan, Italy

    Francesco Peri

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Shimoyama, A., Fukase, K. (2021). Chemically Synthesized TLR4 Ligands, Their Immunological Functions, and Potential as Vaccine Adjuvant. In: Rossetti, C., Peri, F. (eds) The Role of Toll-Like Receptor 4 in Infectious and Non Infectious Inflammation. Progress in Inflammation Research, vol 87. Springer, Cham. https://doi.org/10.1007/978-3-030-56319-6_1

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