title: A combination of the TLR4 agonist CIA05 and alum promotes the immune responses to Bacillus anthracis protective antigen in mice.
abstract: Anthrax is an infectious disease caused by Bacillus anthracis. The currently licensed human anthrax vaccines contain protective antigen (PA) as a major protective component and alum as an adjuvant. In this study, we investigated whether CIA05, a TLR4 agonist, is able to promote the immune response to an anthrax vaccine adjuvanted with alum. BALB/c mice were immunized intraperitoneally three times at 2-week intervals with a recombinant B. anthracis PA alone or in combination with CIA05 in the absence or presence of alum, and immune responses were determined 2 or 3 weeks after the third immunization. The results showed that the combination of CIA05 and alum significantly increased both serum anti-PA IgG antibody and toxin-neutralizing antibody titers, and the adjuvant effects were greater when lower antigen doses were used for immunization. Both CIA05 and alum stimulated PA-specific splenocyte secretion of interleukin (IL)-4, IL-5, and IL-6. A combination of the two yielded synergistic effects on IL-4 secretion, but CIA05 tended to repress IL-5 and IL-6 secretions induced by alum. Co-administration of CIA05 and alum also increased GL7 expression in B220(+)CD24(+) splenic cells, indicating the ability to activate B cells. These data suggest that CIA05, combined with alum, could be used to achieve higher immune responses to PA, leading to the development of an effective anthrax vaccine.
authors.affiliation: Department of Bioscience and Biotechnology, College of Bioscience, Sejong University, 98 Kunja-dong, Kwangjin-gu, Seoul 143-747, Republic of Korea.
authors.forename: Seo Ri
authors.initials: SR
authors.lastname: Wui
authors.forename: Hye Kyeong
authors.initials: HK
authors.lastname: Kim
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Han
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Chun
authors.forename: Yang Je
authors.initials: YJ
authors.lastname: Cho
authors.forename: Na Gyong
authors.initials: NG
authors.lastname: Lee
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020011:Protective Agents / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D000943:Antigens, Differentiation; D001427:Bacterial Toxins; D007074:Immunoglobulin G; D007378:Interleukins; D020011:Protective Agents; D011994:Recombinant Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C030325:anthrax toxin; C096712:antigen GL7; C041524:aluminum sulfate