Oral vaccination with immune stimulating complexes

There is a need for non-living adjuvant vectors which will induce a full ra nge of local and systemic immune responses to orally administered purified antigens. Here we describe our experience with lipophilic immune stimulatin g complexes (ISCOMS) containing the saponin adjuvant Quil A. When given ora lly, ISCOMS containing the model protein antigen ovalbumin (OVA) induce a w ide range of systemic immune responses, including Th1 and Th2 CD4 dependent activity, class I MHC restricted cytotoxic T-cell responses and local prod uction of secretory IgA antibodies. More recent results indicate that ISCOM S may act partly by enhancing the uptake of protein from the gut. In additi on, intraperitoneal injection of ISCOMS recruits and activates many compone nts of the innate immune system, including neutrophils, macrophages, and de ndritic cells. In parallel, there is increased production of nitric oxide ( NO), reactive oxygen intermediates (ROI), interleukins (IL) 1, 6, 12, and g amma interferon (gamma IFN). Of these factors, only IL12 is essential for t he immunogenicity of ISCOMS in vivo, as mucosal and systemic responses to I SCOMS are reduced in IL12KO mice, but not in IL4KO, IL6KO, inducible NO syn thase (iNOS) KO, or gamma IFN receptor KO mice. We propose that ISCOMS act by targetting antigen and adjuvant to macrophages and/or dendritic cells. T his pathway may be amenable to exploitation for vaccine development, especi ally if combined with another vector with a different mucosal adjuvant prof ile, such as cholera toxin. (C) 1999 Elsevier Science B.V. All rights reser ved.