Monophosphoryl Lipid A (MPLA) as Vaccine Adjuvant

Combining an immunological adjuvant with non-infectious vaccine antigens can produce a faster, stronger, and more durable antibody response than the responses achieved by immunization with the antigen alone. Monophosphoryl lipid A is a well-characterized TRIF-biased agonist of TLR4 and has been utilized as adjuvants in some vaccines approved by U.S. FDA. Creative Biolabs is a leader in the field of vaccine development and the extensive experience and expertise of our scientists enable us to provide development services related to innate immune stimulators, particularly the adjuvant development of monophosphoryl lipid A (MPLA).

Monophosphoryl Lipid A (MPLA)

Monophosphoryl lipid A (MPLA) is a low-toxicity agonist of TLR4, which is derived from lipopolysaccharide (LPS) component of gram-negative bacterial cell wall. It may be the first vaccine adjuvant approved for widespread use since alum because it generates clinically useful immune responses and is nearing regulatory approval for use as a human vaccine adjuvant.

The MPL was created in the 1970s by Edgar Ribi, a scientist at the Rocky Mountain Laboratory in the United States. He systematically manipulated the LPS structure of acid and base hydrolysis to develop a detoxified form of 'Coleys Toxin' for cancer treatment. In an early trial, the anti-tumor activity of MPL appeared to be unimpaired relative to its parental LPS, but the inflammatory toxicity was only 0.1%. It is the first and only refined TLR ligand to date which achieves clinical and regulatory success in preventive vaccines against healthy individuals, with high safety expectations. Therefore, MPLA provides an important model for those who attempt to understand how vaccine response is decoupled from adjuvant activity at the level of adaptive priming. The adjuvant effect of MPLA requires TLR4, and though TLR signaling may not be critical for an enhanced antibody response under all conditions, but TLR agonists do show particular promise as cytotoxic T cell-active adjuvants.

The conserved construct of lipid A (1) and the structures of <em>N. meningitidis</em> lipid A (2) and designed MPLA derivatives and their sTn conjugates (3-6).

Fig.1 The conserved construct of lipid A (1) and the structures of N. meningitidis lipid A (2) and designed MPLA derivatives and their sTn conjugates (3-6). (Zhou Z. 2014)

Advantages of MPLA as an Adjuvant for Vaccine Formulation

  • Durable antibody
  • TH1-dependent cytotoxic T cell activity
  • Fewer vaccinations
  • Less injected material

Creative Biolabs is specialized in assisting clients with every stage of the vaccine development services, including adjuvant optimization. As an innovative and truly premier drug discovery and development research partner, Creative Biolabs is committed to providing the best quality services and high level of specialized support.

Reference

  1. Zhou Z, et al. Synthesis and evaluation of monophosphoryl lipid A derivatives as fully synthetic self-adjuvanting glycoconjugate cancer vaccine carriers. Org Biomol Chem. 2014, 12(20): 3238-45.

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