Toll-like receptor 4 (TLR4) recognizes and is activated by the major constituent of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS). Structurally, it consists of a polysaccharide chain (O-antigen) connected to a core region, which is tethered to the bacterial outer membrane by a specific carbohydrate-lipid moiety, lipid A, also known as endotoxin. Based on the structure of the O-antigen LPS can be classified into smooth (S) or rough (R) chemotypes.
Additionally, with the natural removal of one phosphate group from lipid A, monophosphoryl Lipid A (MPLA) is produced. MPLA is a low-toxicity derivative of LPS that retains its immunostimulatory properties. MPLA is widely used as a vaccine adjuvant due to its potent immunomodulatory properties and low inflammatory toxicity. InvivoGen provides MPLA VacciGrade™, a preclinical grade of MPLA guaranteed to be sterile, for use as a vaccine adjuvant.
LPS-derivatives (such as MPLA) can also be made synthetically, to provide more control over the structure of the most potent aspect of the LPS, lipid A. This is especially important for future use as potential vaccine adjuvants.
InvivoGen offers an expanding range of TLR4 agonists including:
- Smooth LPS: purified from a range of bacteria including E. coli
- Rough LPS: purified from E. coli K12
- Natural LPS-derivatives: MPLA purified from Salmonella minnesota R595
- Synthetic LPS-derivatives: chemically-synthesized MPLA and lipid A mimics
InvivoGen also provides two grades of purity for LPS, standard and Ultrapure. The biological function of these TLR4 agonists is validated using HEK-Blue™ TLR4 Cells.