The adjuvanticity of gamma inulin

Abstract

Gamma-inulin (g-IN) is a polymorph identified as the active component of inulin preparations that specifically activates the alternative pathway of complement (APC). The APC is central to many leucocyte functions, including B cell activation. We show here that g-IN, when formulated as a pure, endotoxin-free, fine suspension insoluble at 37 degrees C and given at 50-100 micrograms per mouse, is a potent adjuvant for both humoral and cell-mediated responses to a variety of antigens. g-IN increased secondary IgG responses five- to 28-fold (P less than 0.001), using as antigen phosphorylcholine coupled to keyhole limpet haemocyanin; subclasses IgG 2a, 2b, and 3 were boosted several hundred-fold, IgG 1 10-fold. IgM and IgA were increased four- to six-fold. Delayed hypersensitivity, by footpad swelling after secondary challenge with sheep red blood cells (SRBC), was increased more than two-fold (P less than 0.001) if g-IN was included with the primary SRBC, equivalent to increasing primary doses 10-fold. g-IN was equally active if given 5 days before the primary SRBC. Thus it is an immune stimulant rather than a depot or vehicle for antigen. Mice primed subcutaneously with 30-300 HA units of H2N2 influenza virus (strain A/JAP) and challenged intranasally with a lethal dose of H1N1 virus (strain A/WSN) all died, but if g-IN was given with the primary antigen 50% of the mice survived (P less than 0.001), a deduced but not proven boost to cytotoxic T cell-mediated immunity. Unpublished work has shown that g-IN has no adverse effects at adjuvant-active doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

“…Adjuvancity of inulin was linked to the activation of the complement cascades [50]. Structurally, inulin occurred in various isoforms a, b, g and d. Out of these, g inulin was proven to be a powerful adjuvant in immune activation [18]. More recently, d inulin has been characterized as a more potent adjuvant than the g isoform, enhancing both humoral and cellular immune responses when administrated together with an antigen [51].…”

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

“…The first therapeutic isoform (gamma inulin (GI)) was followed by the more active delta inulin (DI), which is the clinically preferred option . The biological significance of these newer, relatively insoluble inulin forms, in contrast to the more soluble alpha and beta isoforms, is their clinical utility as potent, safe and well-tolerated immune modulators, most notably as vaccine adjuvants (Cooper and Steele 1988;Frazer et al 1999;Silva et al 2004;Lobigs et al 2010;Cooper and Petrovsky 2011;Cristillo et al 2011;Layton et al 2011;Gordon et al 2012;Honda-Okubo et al 2012;Larena et al 2013;Saade et al 2013) but also with anti-cancer effects (Cooper and Carter 1986b;Cooper 1993;Korbelik and Cooper 2007). DI is also a useful reagent for exploring and regulating cellular immune functions in vitro and in vivo.…”

Potentiation of photodynamic therapy of cancer by complement: the effect of γ-inulin

“…Treatment of mice with g-inulin was shown to result in deposition of complement C3-fragments on the surface of macrophages, which enables these antigen-presenting cells (APCs) to greatly increase their efficacy in enhancing the proliferation of antigen-specific T cells (Kerekes et al, 2001). Gamma-inulin is also a powerful adjuvant of the antibody responses (Cooper and Steele, 1988;Silva et al, 2004). Owing to these properties, there is also interest in g-inulin as vaccine adjuvant, its safety for human use has been verified (Frazer et al, 1999).…”