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表达结核分枝杆菌抗原 T 和 B 细胞表位的重组牛分枝杆菌卡介苗克隆的免疫原性。

Immunogenicity of recombinant Mycobacterium bovis bacille Calmette-Guèrin clones expressing T and B cell epitopes of Mycobacterium tuberculosis antigens.

机构信息

School of Health Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

出版信息

BMC Immunol. 2013;14 Suppl 1(Suppl 1):S5. doi: 10.1186/1471-2172-14-S1-S5. Epub 2013 Feb 25.

DOI:10.1186/1471-2172-14-S1-S5
PMID:23458635
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3582440/
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.

摘要

用表达结核分枝杆菌（MTB）Ag85B 抗原的三个 T 细胞表位（P1、P2、P3）与 Mtb8.4 蛋白融合的重组牛分枝杆菌卡介苗（rBCG）（rBCG018）或与 ESAT-6、CFP-10 和 MTP40 蛋白的 B 细胞表位融合的这些抗原的组合（rBCG032）来免疫 Balb/c 小鼠。在用 rBCG032 免疫后，针对 Mtb8.4 抗原和 ESAT-6 和 CFP-10 B 细胞表位测定总 IgG 反应。用 rBCG032 免疫的小鼠对 ESAT-6 和 MTP40（P1）B 细胞表位的 IgG1 和 IgG2a 抗体以及针对两种 P1 和 P2 MTP40 B 细胞表位的 IgG3 显著增加。用 rBCG018 免疫的小鼠的脾细胞针对 Ag85B P2 和 P3 T 细胞表位和 Mtb8.4 蛋白增殖，而用 rBCG032 免疫的小鼠的脾细胞则针对所有 Ag85B 表位和 ESAT-6 B 细胞表位作出反应。用 rBCG018 免疫的小鼠的 CD4+和 CD8+淋巴细胞主要针对 T 细胞表位产生 Th1 型细胞因子。用 rBCG032 获得了针对 T 细胞表位的类似识别模式，同时还识别 ESAT-6、CFP-10 和 MTP40 的一个 B 细胞表位，具有相同的细胞因子模式。这项研究表明，表达 MTB 的 T 或 T 和 B 细胞表位的 rBCG 构建体诱导了针对 MTB 的适当免疫原性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03aa/3582440/6e3381f4ab0b/1471-2172-14-S1-S5-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03aa/3582440/0498e1a5152e/1471-2172-14-S1-S5-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03aa/3582440/6e3381f4ab0b/1471-2172-14-S1-S5-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03aa/3582440/0498e1a5152e/1471-2172-14-S1-S5-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03aa/3582440/6e3381f4ab0b/1471-2172-14-S1-S5-2.jpg

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