Immune-stimulating complexes containing Quil A and protein antigen prime class I MHC-restricted T lymphocytes in vivo and are immunogenic by the oral route.

Induction of all forms of protective immunity by oral immunization with subunit vaccines is an ideal goal for the development of novel vaccines, but creates several theoretical problems from the point of view of antigen processing mechanisms. We show here that incorporation of the protein antigen ovalbumin (OVA) in lipophilic immune-stimulating complexes (ISCOMS) induces very strong primary immune responses in mice and requires very small amounts of antigen. OVA ISCOMS were particularly efficient at stimulating T-cell-mediated immunity in vivo, including delayed-type hypersensitivity (DTH) and potent class I major histocompatibility complex (MHC)-restricted cytotoxic T-cell responses. Furthermore, unlike native protein, OVA in ISCOMS was immunogenic when given orally. Thus, ISCOMS seem to allow protein to enter both the endogenous and exogenous pathways of antigen processing and overcome the usual induction of tolerance after feeding antigen. ISCOMS could provide potentially useful adjuvants for the development of oral subunit vaccines.