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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acyltransferases / immunology
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Acyltransferases / metabolism
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Adjuvants, Immunologic
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Animals
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Antigens, Bacterial / immunology*
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Antigens, Bacterial / metabolism
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BCG Vaccine / genetics
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BCG Vaccine / immunology*
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Bacterial Proteins / immunology
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Bacterial Proteins / metabolism
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cell Proliferation
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Epitopes, B-Lymphocyte / biosynthesis
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Epitopes, B-Lymphocyte / immunology*
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Epitopes, T-Lymphocyte / biosynthesis
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Epitopes, T-Lymphocyte / immunology*
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Immunoglobulin G / immunology
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Mice
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Mice, Inbred BALB C
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Mycobacterium tuberculosis / immunology*
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Recombinant Fusion Proteins / immunology
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Type C Phospholipases / immunology
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Type C Phospholipases / metabolism
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Vaccination
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Vaccines, Synthetic / immunology
Substances
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Adjuvants, Immunologic
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Antigens, Bacterial
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BCG Vaccine
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Bacterial Proteins
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CFP-10 protein (71-85), Mycobacterium tuberculosis
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ESAT-6 protein, Mycobacterium tuberculosis
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Epitopes, B-Lymphocyte
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Epitopes, T-Lymphocyte
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Immunoglobulin G
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Mtb8.4 protein, Mycobacterium tuberculosis
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Peptide Fragments
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Recombinant Fusion Proteins
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Vaccines, Synthetic
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Mycobacterium tuberculosis antigens
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Acyltransferases
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antigen 85B, Mycobacterium tuberculosis
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Type C Phospholipases
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MpcA protein, Mycobacterium tuberculosis