MPLA Synthetic - TLR4 Agonist

TLR4 Agonist - Synthetic monophosphoryl lipid A

Synthetic lipid A from E. coli serotype R515 (MPLAs) is a monophosphoryl lipid A with 6 fatty acyl groups. It is structurally very similar to natural MPLA except that natural MPLA contains a mixture of 5, 6, and 7 acyl lipid A. The number of fatty acids is a major determinant of the immunogenicity of endotoxin.

Synthetic E. coli lipid A activates TLR4 but does not activate TLR2 even at high concentrations, reflecting its high purity. This product can be used for immunomodulatory studies as it is a pure monophosphoryl lipid A containing 6 fatty acyl groups. 

InvivoGen also offers MPLA Synthetic VacciGrade™, a high-quality pre-clinical grade suited for in vivo studies.

Background

Monophosphoryl Lipid A (MPLA) is a low-toxicity derivative of lipopolysaccharide (LPS) that retains the immunologically active lipid A portion of the parent molecule. Both LPS and MPLA are TLR4 agonists, but they signal through different adaptors, MyD88 and TRIF, respectively^{1, 2}. The reduced toxicity of MPLA is attributed to the preferential recruitment of TRIF upon TLR4 activation, resulting in decreased induction of inflammatory cytokines. MPLA is widely used as a vaccine adjuvant due to its potent immunomodulatory properties and low inflammatory toxicity^{1, 2}. 

1. Sastry M. et al., 2017. Adjuvants and the vaccine response to the DS-Cav1stabilized fusion glycoprotein of respiratory syncytial virus. PLoS One. 12(10):e0186854.
2. Cui W. et al., 2014. TLR4 ligands lipopolysaccharide and monophosphoryl lipid a differentially regulate effector and memory CD8+ T Cell differentiation. J Immunol. 192(9):4221-32.
3. Steimle A. et al., 2017. Structure and function: Lipid A modifications in commensals and pathogens. Int J Med Microbiol. 306(5):290-301.