IMMUNE-STIMULATING COMPLEXES AS ADJUVANTS FOR INDUCING LOCAL AND SYSTEMIC IMMUNITY AFTER ORAL IMMUNIZATION WITH PROTEIN ANTIGENS

Orally active synthetic vaccines containing purified antigens would ha ve many benefits for immunizing against systemic and mucosal diseases. However, several factors have limited the development of such vaccine s, including the poor immunogenicity of purified proteins and their us ual ability to induce tolerance when given orally. Here, we show that incorporation of ovalbumin (OVA) into immune-stimulating complexes (IS COMS) containing saponin prevents the induction of oral tolerance in m ice. In parallel, the spleen and mesenteric lymph node of mice fed OVA ISCOMS are primed for class I major histocompatibility complex (MHC)- restricted cytotoxic T-cell activity which recognizes physiologically processed epitopes on OVA. Oral immunization with OVA ISCOMS also stim ulates high secretory IgA antibody responses in the intestine itself, as well as serum IgG antibodies. None of these active immune responses are detectable in mice fed OVA alone. Despite the potent priming of m ucosal priming by OVA ISCOMS, re-exposure to antigen does not induce t he intestinal immunopathology found in other systems after the breakdo wn of oral tolerance. Thus, ISCOMS have several unique properties as v ectors for oral immunization and could provide a basis for future muco sal vaccines.