Immunostimulating complexes (ISCOMs) for nasal vaccination

The immunostimulating complex (ISCOM) is documented as a strong adjuvant an d delivery system for parenteral immunization. Its effectiveness for mucosa l immunization has also been proven with various incorporated antigens. Lov gren et al. were the first to demonstrate the capacity of influenza virus I SCOMs to induce mucosal immune response and protection after one comparativ ely low nasal dose. Further studies show that similar to Cholera toxin (CT) and Escherichia coli heat-labile toxin (LT), ISCOMs break immunological to lerance and exert strong mucosal adjuvant activity, resulting in secretory IgA and systemic immune responses. Striking is the capacity of ISCOMs to in duce CTL response also after nasal administration. In contrast to CT, ISCOM s initiate mucosal as well as systemic immune responses in an IL-12 depende nt manner but independently of IL-4. The recombinant B subunit of cholera t oxin (rCTB) was incorporated in the same ISCOM particle to explore symbioti c effects. The IgA response to rCTB in lungs was increased 100-fold when rC TB was administered nasally in ISCOMs and more than 10-fold in the remote m ucosa of the genital tract. An enhanced IgA response to a passenger antigen OVA was recorded in the remote genital tract. After i.n. administration of the envelope proteins of respiratory syncytial virus in ISCOMs, high serum antibodies were induced, almost at the same levels as those following pare nteral immunization and potent IgA responses were also evoked both at the l ocal respiratory mucosa, and in the cases tested at the distant mucosae of the genital and intestinal tracts. Similar results have also been recorded with ISCOMs containing envelope proteins from Herpes simplex virus, Influen za vir-us and Mycoplasma mycoides. The mucosal targeting property of envelo pe proteins of RSV was utilized in an HIV-gp 120 RSV ISCOM formulation. Aft er nasal administration an enhanced mucosal IgA response to gp120 was obser ved in the female reproductive tract. In general, antigens derived from env elope viruses or cell membranes incorporated into ISCOMs retain their biolo gical activity and conformation, encompassing the mucosal targeting and vir us neutralizing properties. (C) 2001 Elsevier Science B.V. All rights reser ved.