ABSTRACT
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-gamma 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.
Subject(s)
Adjuvants, Immunologic/pharmacology , Cysteine Endopeptidases/pharmacology , Immunity, Mucosal/drug effects , Lipopolysaccharides/pharmacology , Vaccines/immunology , Administration, Intranasal , Animals , Antibodies, Viral/analysis , Antibodies, Viral/biosynthesis , Chemistry, Pharmaceutical , Cytokines/analysis , Cytokines/biosynthesis , Drug Carriers , Drug Combinations , Female , Hemagglutinins/analysis , Hemagglutinins/immunology , Immunoglobulin A/analysis , Immunoglobulin A/biosynthesis , Immunoglobulin G/analysis , Immunoglobulin G/biosynthesis , Influenza Vaccines/therapeutic use , Lipopolysaccharides/immunology , Liposomes , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/prevention & control , Spleen/cytology , Vaccines/administration & dosage , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunologyABSTRACT
The potential for enhancing the immunogenicity of recombinant (baculovirus-derived) influenza hemagglutinin (rHA) was investigated by comparing the immune responses elicited in mice by an intranasal (i.n.) rHA formulated with Proteosomes, with those induced by intramuscular (i.m.) or i.n. rHA alone. The Proteosome-rHA vaccine induced mucosal responses in the respiratory tract, as well as high serum IgG and hemagglutination inhibition (HAI) titers. In contrast, rHA alone given i.m. induced serum IgG without mucosal responses and was ineffective at inducing either mucosal or systemic responses when given i.n. Only mice immunized with the Proteosome-rHA vaccine were completely protected from both death and acute morbidity following live virus challenge, indicating that the i.n. Proteosome-rHA vaccine induced more complete protective immunity than the same doses of unformulated rHA given i.n. or i.m.
