Lipopeptides as immunoadjuvants and immunostimulants in mucosal immunization

In previous studies we have shown that lipopeptides constitute potent immun oadjuvants in mice, rabbits and other species: in parenteral immunization, lipopeptide adjuvants were comparable, or in some cases superior to Freund' s adjuvant, and were devoid of the side effects of this additive. Here we d emonstrate that lipopeptides also constitute adjuvants for mucosal immuniza tions. The serum antibody responses against the wheat storage protein gliad in, the bee venom constituent melittin, or the hen egg protein ovalbumin co uld in most cases be enhanced more than 100-fold by the lipopeptide P3CSK4, applied via the nasal route. An enhanced specific antibody level could als o be detected in supernatants of cell cultures prepared from spleens, Peyer s patches, lungs and mesenteric lymph nodes of immunized mice. Moreover, th e lipopeptide P3CSK4 enhanced chemiluminescence in mouse spleen cells and p eritoneal macrophages in vitro, indicating a macrophage-activating effect. Finally, nasal application of lipopeptide increased protection against a le thal infection of influenza. Our findings are of importance for the improve ment of immunizations and might lead to more effective vaccines.