The adjuvanticity of gamma inulin.
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 Unpublished work has shown that g-IN has no adverse effects at adjuvant-active doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Cooper
P D
PD
Division of Virology and Cellular Pathology, John Curtin School of Medical Research, Australian National University, Canberra, ACT.
Steele
E J
EJ
D000276:Adjuvants, Immunologic; D000818:Animals; D003170:Complement Pathway, Alternative; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006968:Hypersensitivity, Delayed; D007136:Immunoglobulins / Q000096:biosynthesis; D007444:Inulin / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009975:Orthomyxoviridae / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D007444:Inulin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin