Immune stimulating complexes as mucosal vaccines.
There is a need for non-living adjuvant vectors that will allow a full range of local and systemic immune responses to orally administered purified antigens. Here we describe our experience with lipophilic immune-stimulating complexes (ISCOMs) containing the saponin adjuvant Quil A. When given orally, ISCOMs containing the model protein antigen ovalbumin (OVA) induce a wide range of systemic immune responses, including Th1 and Th2 CD4-dependent activity, serum IgG antibodies and class I MHC-restricted cytotoxic T cell responses. In addition, there is local production of secretory IgA antibodies in the intestine itself, as well as priming of CD4 and CD8 T cell responses in the draining lymphoid tissues. Preliminary results indicate that the mucosal adjuvant properties of ISCOMs may reflect their ability to deliver antigen combined with the pro-inflammatory properties of Quil A in a particulate form. Of the many inflammatory mediators induced, interleukin-12, derived from dendritic cells and/or macrophages, appears to be of central importance. These results indicate that ISCOMs may prove to be useful mucosal vaccine vectors with functions which are distinct from existing vectors of this type.
Department of Immunology, University of Glasgow, Western Infirmary, Scotland.
R E
RE
Smith
A M
AM
Donachie
A M
AM
Mowat
D000818:Animals; D006801:Humans; D016882:ISCOMs / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D014611:Vaccination / Q000379:methods / Q000639:trends
D016882:ISCOMs