Current Status of Toll-Like Receptor 4 Ligand Vaccine Adjuvants

Toll-like receptor (TLR) 4 ligands represent a unique class of adjuvant molecules. Among the few types of adjuvants employed in products approved for human use, only appropriately formulated TLR4 ligands have been shown to activate a specific pattern recognition receptor, initiating a specific and relatively well-defined mechanism of action. No other TLR ligand–based class of adjuvant is as nearly advanced in terms of clinical product development. Herein, we provide a product-focused update on the clinical and preclinical development progress of TLR4-based adjuvant formulations, highlighting the critical role of formulation effects on TLR4 ligand bioactivity. Adjuvant formulations based on TLR4 ligands are likely to play an increasingly integral role in the successful development of new vaccines against infectious and chronic indications.