Glucopyranosyl Lipid A (GLA) as Vaccine Adjuvant

Protein-based vaccines are safe and cost-effective but have poor immunogenicity, which require adjuvants to help induce immunity. As a synthetic TLR4 agonist, Glucopyranosyl Lipid A (GLA) is a highly potent adjuvant and can greatly enhance humoral and cellular immune responses. 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 Glucopyranosyl lipid A.

Glucopyranosyl Lipid Adjuvant (GLA)

Triggering TLR4 on the cell surface of antigen-presenting cells is an essential pathway for inducing innate and adaptive immune responses. New generations of TLR4 agonists are being developed, including synthetic lipid A-like molecules such as glucopyranose lipid adjuvant, that are more receptor-specific, have fewer side effects but retain or increase adjuvant activity. Glucopyranosyl Lipid Adjuvant, a new synthetic lipid A derivative, is composed of a disaccharide backbone, a single phosphate group, and six C14 acyl chains. It is a TLR4 agonist and a highly effective adjuvant that greatly enhances humoral and cellular immune responses. GLA can be synthesized as single chemical entities of high purity and can be chemically modified in a defined manner to enhance the biological activity.

Differences between the synthetic GLA (structure in grey) and naturally occurring endotoxins.

Fig.1 Differences between the synthetic GLA (structure in grey) and naturally occurring endotoxins. (Coler RN. 2011)

GLA as a Vaccine Adjuvant

Innate immune response based on a vaccine adjuvant of lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, is driven by TLR4 and adaptor proteins including MyD88 and TRIF, resulting in the production of inflammatory cytokines, type I interferons, and chemokines. GLA has multifunctional immunomodulatory activities similar to naturally-derived monophosphate lipid A (MPL) on mouse DC, including the production of inflammatory cytokines, chemokines, DC maturation, and antigen-presenting functions. GLA adjuvants have been found to stimulate and direct innate and adaptive immune responses by inducing DC maturation and releasing pro-inflammatory cytokines and chemokines associated with immune cell trafficking, which is important to guide the development of future vaccine adjuvants. GLA has been formulated as a proprietary stable oil-in-water emulsion (GLA-SE) and in aqueous form. It has shown good safety when used in conjunction with the monkey flu vaccine and a recently completed Phase I trial.

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. Coler RN, et al. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One. 2011, 6(1): e16333.

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