The adjuvanticity of gamma inulin

Summary 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°C and given at 50–100 μg 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 <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 <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 HIN1 virus (strain A/WSN) all died, but if g‐IN was given with the primary antigen 50% of the mice survived( P < 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 Unpublished work has shown that g‐IN has no adverse effects at adjuvant‐active doses. g‐IN is thus a promising new vaccine adjuvant. It also has a potential for antitumour therapy, and is a specific reagent for expioring the role of complement in vivo .