Adjuvants containing natural and synthetic Toll-like receptor 4 ligands

Abstract

The last decade has seen an increased focus on the development of adjuvants for vaccines, and several novel adjuvants are now in licensed products or in late-stage clinical development. These advancements have been aided by the discovery of receptors and signaling pathways of the innate immune system and an increased understanding of how these innate responses influence the adaptive immune response. Successful vaccine development relies on knowledge of which adjuvants to use and the proper formulation of adjuvants and antigens to achieve safe, stable and immunogenic vaccines. In this review, the authors focus on the current use of natural and synthetic lipopolysaccharide analogues that retain their adjuvant properties with reduced toxicity compared with the parent compound for use in emerging vaccines. The authors review how these compounds initiate signal transduction through Toll-like receptor 4, insights from structure–function studies and how formulation parameters can influence their effectiveness as vaccine adjuvants.

Keywords::

• formulation
• glucopyranosyl lipid A
• lipopolysaccharide
• monophosphoryl lipid A
• pattern recognition receptors
• Toll-like receptor 4
• Toll-like receptor 4 agonist
• vaccine adjuvant

Financial & competing interests disclosure

This work was funded in part by NIH grant 1U01-AI078054 and grant 42387 from the Bill and Melinda Gates Foundation. SG Reed has stock ownership and holdings in Immune Design Corporation. 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.