Chemical Synthesis and Immunological Functions of Bacterial Lipid A for Vaccine Adjuvant Development and Bacterial-Host Chemical Ecology Research

Abstract

Lipopolysaccharide (LPS), an outer membrane component of gram-negative bacteria, is a representative immune activator, and its active principle is the glycolipid lipid A; thus, LPS is a potential adjuvant candidate. However, canonical Escherichia coli LPS is known to be an endotoxin, as it can induce lethal sepsis due to a hyperinflammatory immune response. Therefore, to apply them as adjuvants, it is necessary to structurally modify LPS and lipid A to minimize their toxic effects while maintaining their adjuvant effects Chemical ecology research considers the various life phenomena that occur between organisms as molecular interactions and has mainly focused on plants. Recently, as a new trend, the author hypothesized that LPS and lipid A mediate the bacterial-host chemical ecology and regulate various biological phenomena in the host, especially immunity. The author also predicted that parasitic and symbiotic bacteria that inhabit their hosts would have a low-toxicity immunomodulator owing to chemical structural changes in LPS as a result of co-evolution with the host. To confirm these hypotheses and apply lipid A to low-toxicity and safe adjuvants, the author researched the chemical synthesis and functional evaluation of lipid As. In this chapter, chemical synthesis of lipid A, its structure–activity relationship, and its potential as a vaccine adjuvant are discussed.