title: Immune responses induced by heterologous boosting of recombinant bacillus Calmette-Guerin with Ag85B-ESAT6 fusion protein in levamisole-based adjuvant.
abstract: In the present study, we evaluated the effectiveness of a levamisole-based adjuvant (ADL) to enhance the ability of the Ag85B-ESAT6 fusion protein to boost immune responses after primary vaccination with recombinant bacillus Calmette-Guerin (rBCG) in Balb/c mice. The results were compared with that of the control adjuvant formulation of dimethyl dioctadecylammonium bromide (DDA) and monophosphoryl lipid A (MPL), which has previously been shown to induce T-helper type 1 (Th1)-biased responses. Enzyme-linked immunospot (ELISPOT) assay with Ag85B and ESAT6 derived peptides corresponding to CD4+ and CD8+ T cell restricted epitopes and cell surface immunostaining indicated that Ag85B-ESAT6/ADL predominantly triggered activation of CD4+ T cells. Functional CD8+ T cells with interferon (IFN)-γ production or cytotoxicity were undetectable all vaccinated mice. The ADL adjuvant modified T-helper (Th) subtypes by up-regulating multiple signature cytokines. Furthermore, profiles of the immunoglobulin G (IgG) subtypes indicated ADL enhanced the secretion of Th1-associated IgG2a antibodies and decreased the yield of Th2-associated IgG1 subtype. These observations suggest that the ADL adjuvant formulated with a protein booster may induce Th1-biased cellular and humoral immune responses to primary vaccination with a live attenuated bacterial TB vaccine.
authors.affiliation: National Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin University, Jilin, P. R. China 130012. chysx6@163.com
authors.forename: Qingrui
authors.initials: Q
authors.lastname: You
authors.forename: Yongge
authors.initials: Y
authors.lastname: Wu
authors.forename: Dehua
authors.initials: D
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
authors.forename: Xizhen
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000378:metabolism; D007978:Levamisole / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control; D000099192:CD69 Antigens
chemical_list: D000217:Acyltransferases; D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001500:BCG Vaccine; D001426:Bacterial Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D007371:Interferon-gamma; D037181:Lectins, C-Type; D007978:Levamisole; D011993:Recombinant Fusion Proteins; D000099192:CD69 Antigens; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C112580:antigen 85A, Mycobacterium tuberculosis