PRESERVATION OF MUCOSAL AND SYSTEMIC ADJUVANT PROPERTIES OF ISCOMS INTHE ABSENCE OF FUNCTIONAL INTERLEUKIN-4 OR INTERFERON-GAMMA

Adjuvants are a critical component of non-viable vaccine vectors, part icularly for those to be used via mucosal routes, Although most, adjuv ants act by inducing local inflammatory responses, the molecular basis of many of these effects is unclear. Here we have investigated whethe r interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) are required f or the induction of local and systemic immune responses by oral and pa renteral administration of ovalbumin (OVA) in immune stimulating compl exes (ISCOMS), a potent mucosal adjuvant vector. Our results show that after oral or systemic immunization with OVA ISCOMS, IL-4 knockout (I L4KO) and IFN-gamma receptor knockout (IFN-gamma RKO) mice develop an entirely normal range of immune responses including delayed-type hyper sensitivity (DTH), serum immunoglobulin G (IgG) antibodies, T-cell pro liferation and cytokine production, class I major histocompatibility c omplex (MHC)-restricted cytotoxic T lymphocyte (CTL) activity and inte stinal ISA antibodies. These responses were of a similar magnitude to those found in the wild-type mice, indicating that the immunogenicity of ISCOMS is not influenced by the presence of IL-4 or IFN-gamma and e mphasizing the potential of ISCOMS as widely applicable mucosal adjuva nts.