Vaccine adjuvants based on gamma inulin.
Algammulin and gamma-IN comprise a novel class of vaccine adjuvant. Their use in vaccines is to exploit the humoral defense known as the alternative pathway of complement. They use a "natural" mechanism and the biochemical basis of their action is well understood in general terms. They are fully researched up to the stage of specific commercial application. Inulin itself is registered for human use as a solution and is without physiological effect except for ACP activation as gamma-IN particles. The ACP comprises a relatively harmless part of the inflammatory response. Gamma inulin is nontoxic in several species including humans and is nonpyrogenic. The amount of systemic C3a produced from adjuvant-active doses of gamma-IN is expected to be very much less than that routinely tolerated without effect by human renal dialysis patients. Registration of gamma-IN should not be difficult. Gamma inulin in vivo is either dissolved and excreted unchanged or metabolized to simple foodstuffs. Its primary chemical structure is completely known, and it is inexpensive, readily available, and easy to handle and manufacture. It is completely stable under normal conditions of use and storage. Patent cover is either fully granted or accepted for granting in most developed countries. Alum is also registered for human use and its combination with gamma-IN known as Algammulin is equally nontoxic especially in the fine formulation, and is equally stable. The partial coating with inulin in Algammulin greatly reduces the undesirable effects of alum such as granuloma formation and IgE generation. Combinations of gamma-IN with immunogen carriers other than alum are feasible, either as hybrid particles or as simple mixtures of particles of similar size. Gamma inulin, and especially Algammulin, are potent enhancers of the Th1 immune response pathway, boosting seroconversion rates and immunological memory in protective Ab classes and enhancing cell-mediated immunity. The responses can equal those of CFA. They are also Th2 pathway enhancers, especially for IgA, and the emphasis on Th2 might be varied by altering the alum-to-inulin ratio in the final formulation. A dual response (balanced Th1 and Th2) may be desirable for several reasons. Their primary targets in vivo are probably lymphocytes rather than macrophages. Gamma inulin-based adjuvants therefore comprise new, safe, potent, and attractive candidates for enhancing responses to human and veterinary vaccines, especially those requiring cell-mediated defenses.
Cooper
P D
PD
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds; D000535:Aluminum / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D003167:Complement Activation / Q000187:drug effects; D004338:Drug Combinations; D006801:Humans; D007444:Inulin / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology
D000276:Adjuvants, Immunologic; C070342:Algammulin; D000534:Alum Compounds; D004338:Drug Combinations; D007444:Inulin; D000535:Aluminum