Delta inulin: a novel, immunologically active, stable packing structure comprising  -D-[2 -> 1] poly(fructo-furanosyl)  -D-glucose polymers

Abstract

We report a novel isoform of β-D-[2 → 1] poly(fructo-furanosyl) α-D-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37-48°C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56°C, whereas GI is converted from AI at 45°C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity.

Differentially expressed proteins in the blood serum of piglets in response to a diet supplemented with inulin

“…Taken together, these findings may indicate that the increased expression of VT observed in the present study, may protect the piglet organism against excessive cytolytic action of activated complement. The studies of Cooper (1995) and Cooper and Petrovsky (2011) clearly indicate that γ and δ inulin have the ability to activate the alternative complement pathway via activation of the complement C3 receptors localised on the surface of macrophages.…”

An Inactivated Cell Culture Japanese Encephalitis Vaccine (JE-ADVAX) Formulated with Delta Inulin Adjuvant Provides Robust Heterologous Protection against West Nile Encephalitis via Cross-Protective Memory B Cells and Neutralizing Antibody

“…Advax adjuvant is based on immunologically active delta inulin microparticles (21) and has proved successful in both animal studies and human vaccine trials (22). In preclinical models, Advax was shown to enhance the immunogenicity of a broad range of viral vaccines, including pandemic influenza virus (23), HIV (24), hepatitis B virus (25), African horse sickness virus (26), and JEV (18,27).…”

JE-ADVAX Vaccine Protection against Japanese Encephalitis Virus Mediated by Memory B Cells in the Absence of CD8+T Cells and Pre-Exposure Neutralizing Antibody

“…However, JE-VAX remains the "gold standard" for immunogenicity and safety comparisons of new-generation vaccines against JE (8). Using JE-VAX as a comparator, we showed that JE-ADVAX, a Vero cell culture-grown inactivated JEV antigen (ccJE) (9), combined with Advax, a novel polysaccharide adjuvant derived from delta inulin (10), provided immunogenicity greatly superior to that of JE-VAX in mice and horses (11). In the same study, we also found that JE-ADVAX elicited levels of neutralizing antibody against serologically related flaviviruses of medical significance (West Nile and Murray Valley encephalitis viruses) that were indicative of cross-protective immunity, because they exceeded the titers against the homologous virus (JEV) generated by immunization with the gold standard JE-VAX (11).…”