E6020: a synthetic Toll-like receptor 4 agonist as a vaccine adjuvant.
Safe and cost-effective adjuvants are a critical component to enhance the efficacy of subunit vaccines. Studies have demonstrated that modified natural lipid As derived from enterobacterial lipopolysaccharides, which are agonists of Toll-like receptor 4, are beneficial to vaccine performance. The synthetic phospholipid dimer, E6020, mimics the physicochemical and biological properties of many of the natural lipid As derived from gram-negative bacteria. Similar to its natural counterparts, E6020, which was discovered and developed by Eisai, agonizes Toll-like receptor 4, albeit in an attenuated fashion, eliciting an immunostimulatory response that is conducive to use as a vaccine adjuvant. The derivation of E6020, along with physicochemical properties and in vitro and in vivo studies of immunostimulation and adjuvant activity, are reviewed as a background to its imminent assessment in the clinic.
Ishizaka
Sally T
ST
Eisai Research Institute, 4 Corporate Drive, Andover, MA 01742, USA. sally_ishizaka@eri.eisai.com
Hawkins
Lynn D
LD
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D006801:Humans; D010743:Phospholipids / Q000008:administration & dosage / Q000737:chemistry*; D051197:Toll-Like Receptor 4 / Q000008:administration & dosage / Q000737:chemistry*; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry*
D000276:Adjuvants, Immunologic; C000617976:ER-804053; D010743:Phospholipids; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014612:Vaccines