E6020: a synthetic Toll-like receptor 4 agonist as a vaccine adjuvant

Abstract

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.

Keywords::

• E6020
• lipid A
• lipopolysaccharide synthetic vaccine adjuvant Toll-like receptor 4

Acknowledgements

The authors would like to acknowledge the expertise of Jeffrey Rose, Melinda Genest, Hongsheng Cheng, Diana Liu, Jesse Chow and Donna Young in providing data presented here.

Financial & competing interests disclosure

The authors are solely affiliated with Eisai Research Institute of Boston, Inc., a company fully owned by Eisai Co., Ltd. All patents received or pending are the property of Eisai Co., Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.