Protollin™ is a novel adjuvant comprising Proteosomes™ non-covalently complexed with LPS. Intranasal immunization of mice with Protollin™ combined with detergent-split influenza antigens (HA) or recombinant influenza hemagglutinin (rHA) enhanced serum IgG and mucosal IgA levels by up to 250-fold compared with immunization with the antigens alone. IFN-γ responses were also enhanced compared to the levels produced by splenocytes from mice immunized with antigen alone, while production of IL-5 was abrogated. Mice immunized with Protollin™-rHA were completely protected against lethal challenge with influenza virus, demonstrating that Protollin™ is an effective mucosal adjuvant for prophylactic vaccines.