title: Immunogenicity of recombinant Mycobacterium bovis bacille Calmette-Guèrin clones expressing T and B cell epitopes of Mycobacterium tuberculosis antigens.
abstract: Recombinant Mycobacterium bovis bacille Calmette-Guèrin (rBCG) expressing three T cell epitopes of Mycobacterium tuberculosis (MTB) Ag85B antigen (P1, P2, P3) fused to the Mtb8.4 protein (rBCG018) or a combination of these antigens fused to B cell epitopes from ESAT-6, CFP-10 and MTP40 proteins (rBCG032) were used to immunize Balb/c mice. Total IgG responses were determined against Mtb8.4 antigen and ESAT-6 and CFP-10 B cell epitopes after immunization with rBCG032. Mice immunized with rBCG032 showed a significant increase in IgG1 and IgG2a antibodies against ESAT-6 and MTP40 (P1) B cell epitopes and IgG3 against both P1 and P2 B cell epitopes of MPT40. Splenocytes from mice immunized with rBCG018 proliferated against Ag85B P2 and P3 T cell epitopes and Mtb8.4 protein whereas those from mice-immunized with rBCG032 responded against all Ag85B epitopes and the ESAT-6 B cell epitope. CD4⁺ and CD8⁺ lymphocytes from mice immunized with rBCG018 produced primarily Th1 type cytokines in response to the T cell epitopes. Similar pattern of recognition against the T cell epitopes were obtained with rBCG032 with the additional recognition of ESAT-6, CFP-10 and one of the MTP40 B cell epitopes with the same pattern of cytokines. This study demonstrates that rBCG constructs expressing either T or T and B cell epitopes of MTB induced appropriate immunogenicity against MTB.
authors: School of Health Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors: Rohimah
authors: R
authors: Mohamud
authors: Maryam
authors: M
authors: Azlan
authors: Daniel
authors: D
authors: Yero
authors: Nadine
authors: N
authors: Alvarez
authors: Maria E
authors: ME
authors: Sarmiento
authors: Armando
authors: A
authors: Acosta
authors: Mohd-Nor
authors: MN
authors: Norazmi
mesh_terms: D000217:Acyltransferases / Q000276:immunology / Q000378:metabolism; D000276:Adjuvants, Immunologic; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018985:Epitopes, B-Lymphocyte / Q000096:biosynthesis / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology; D010738:Type C Phospholipases / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C489634:CFP-10 protein (71-85), Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; C114074:Mtb8.4 protein, Mycobacterium tuberculosis; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C072681:Mycobacterium tuberculosis antigens; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis; D010738:Type C Phospholipases; C101028:MpcA protein, Mycobacterium tuberculosis