Brucella spp. lumazine synthase: a novel adjuvant and antigen delivery system to effectively induce oral immunity

• Published in: Microbes and infection Vol. 8; no. 5; pp. 1277 - 1286
• Main Authors: Rosas, Gabriela, Fragoso, Gladis, Ainciart, Natalia, Esquivel-Guadarrama, Fernando, Santana, Angélica, Bobes, Raúl J., Ramírez-Pliego, Oscar, Toledo, Andrea, Cruz-Revilla, Carmen, Meneses, Gabriela, Berguer, Paula, Goldbaum, Fernando A., Sciutto, Edda
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier SAS 01.04.2006; Amsterdam Elsevier; Paris
• Subjects: Adjuvant; Adjuvants, Immunologic - administration & dosage; Administration, Oral; Animals; Antibodies, Helminth - blood; Antigen delivery; Antigens, Helminth - administration & dosage; Antigens, Helminth - chemistry; Antigens, Helminth - genetics; Antigens, Helminth - immunology; Applied microbiology; Bacteriology; Biological and medical sciences; Brucella; Brucella - enzymology; Cysticercosis - immunology; Cysticercosis - prevention & control; Cytokines - metabolism; Female; Fundamental and applied biological sciences. Psychology; Humans; Immunity, Mucosal; Lumazine synthase; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Mucosal immunity; Multienzyme Complexes; Oral vaccine; Peyer's Patches - immunology; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - immunology; Taenia - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; GALT, gut associated lymphoid tissue; Mucosal immunity; Antigen delivery; PPs, Peyer's patches; Oral vaccine; Adjuvant; BLS , Brucella spp. lumazine synthase; Lumazine synthase; CT, cholera toxin; Enzyme; Brucella; Vaccine; Synthase; Antigen; Local immunity; Brucellaceae; Immunological adjuvant; Bacteria
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2005.12.006

Brucella lumazine synthase (BLS) has been previously used with success as a delivery system for systemic immunization against murine cysticercosis. We herein determined the usefulness of BLS as a new antigen-delivery system and mucosal-adjuvant using KETc1, one of the peptides of the anti-cysticercosis vaccine. A protection of up to 98% was induced when KETc1 was used as a chimera fused to BLS. Used as adjuvant of KETc1, BLS also induced a high level of protection (79%), which did not significantly differ from that induced by the cholera toxin (74%). KETc1 and BLS administered separately also reduced the parasite load. KETc1 administered orally as a chimera, and to a lesser extent with BLS as adjuvant, elicited IgG and IgA specific antibodies, which were detectable both in fecal extracts and in sera, and increased B and CD4 activated cells. BLS-KETc1 also increased the levels of transcription of TNF-α, IL-2 and IFNγ in Peyer's patches, and in spleen, only increased TNF-α was observed. Overall, these results showed that BLS can be used as both an antigen-carrier and as an adjuvant in the design of new oral subunit vaccines.