Synthetic lipid A

Synthetic lipid A from E. coli, serotype R515 (MPLAs) is a pure monophosphoryl lipid A compound produced by chemical synthesis.
MPLAs activates TLR4 but does not activate TLR2 reflecting its high purity. MPLAs contains 6 fatty acyl groups, while MPLA purified from bacteria contains a mixture of 5, 6, and 7 acyl lipid A.

MPLA has been tested as an adjuvant in mice and reported to induce a strong Th1 response.

MPLAs VacciGrade™ is suitable for preclinical studies. It is prepared under strict aseptic conditions. It is guaranteed sterile.

MPLAs VacciGrade™ is for research use only, not for use in humans.

Specifications

Specificity: TLR4 agonist - Th1 response

Working concentration: 2- 20 μg/mouse

Quality: Sterile

Molecular weight: 1763.47

CAS Number: 1246298-63-4

Solubility: 1 mg/ml in DMSO

Quality control:

• MPLAs VacciGrade™ is a preclinical grade.

• It is prepared under strict aseptic conditions.

• MPLAs VacciGrade™ is guaranteed sterile.

Contents

MPLAs VacciGrade™ is provided as a clear, lipidic film.

• 1 mg MPLAs VacciGrade™

• 10 ml sterile endotoxin-free physiological water (NaCl 0.9%)

 MPLAs VacciGrade™ is shipped at room temperature.

 Store at -20?C.

 Product is stable 1 year when properly stored.

Upon resuspension, prepare aliquots of MPLAs VacciGrade™ and store at -20?C.

Resuspended product is stable 6 months when properly stored.

Avoid repeated freeze-thaw cycles.

Details

MPLA is a low-toxicity derivative of lipopolysaccharide (LPS), that retains the immunologically active lipid A portion of the parent molecule [1]. While the toxicity associated with LPS prohibits its potential clinical use, MPLA is being developed as a vaccine adjuvant [2]. Both LPS and MPLA are TLR4 agonists, but they signal through different adaptors, MyD88 and TRIF, respectively. The reduced toxicity of MPLA is attributed to the preferential recruitment of TRIF upon TLR4 activation, resulting in decreased induction of inflammatory cytokines [3].

MPLA has been tested as an adjuvant in mice and reported to induce a strong Th1 response [4-5]. Although the mechanism of action of MPLA has not been fully eludicated, it has been suggested that MPLA improves vaccine immunogenicity by enhancing antigen presenting cell maturation [6].

1. Okemoto K. et al., 2006. A potent adjuvant monophosphoryl lipid A triggers various immune responses, but not secretion of IL-1beta or activation of caspase-1. J Immunol. 176(2):1203-8.
2. Casella CR. et al., 2008. Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant. Cell Mol Life Sci. 65(20):3231-40.
3. Mata-Haro V. et al., 2007. The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4. Science. 316(5831):1628-32.
4. Fransen F. et al., 2007. Agonists of Toll-like receptors 3, 4, 7, and 9 are candidates for use as adjuvants in an outer membrane vaccine against Neisseria meningitidis serogroup. Infect Immun. 75(12) :5939-46.
5. Rhee EG. et al., 2010. TLR4 Ligands Augment Antigen-Specific CD8+ T Lymphocyte Responses Elicited by a Viral Vaccine Vector. J. Virol. 84: 10413 - 10419.
6. Didierlaurent A. et al., 2009. AS04, an aluminum salt- and TLR4 agonistbased adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. J Immunol 183(10): 6186-97.

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