Mycobacterium tuberculosis Culture Filtrate Proteins plus CpG Oligodeoxynucleotides Confer Protection to Mycobacterium bovis BCG-Primed Mice by Inhibiting Interleukin-4 Secretion
Mycobacterium tuberculosis Culture Filtrate Proteins plus CpG Oligodeoxynucleotides Confer Protection to Mycobacterium bovis BCG-Primed Mice by Inhibiting Interleukin-4 Secretion
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DOI：
10.1128/iai.00580-09
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发表时间：
2009-12-01
影响因子：
3.1
通讯作者：
Deperon Bonato, Vania Luiza
中科院分区：
文献类型：
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作者：
da Fonseca, Denise Morais;Silva, Celio Lopes;Deperon Bonato, Vania Luiza
培养滤液蛋白（CFP）是结核病疫苗开发的潜在靶点。我们之前表明，尽管CFP加CpG寡聚脱氧核苷酸（CFP/CpG）同源免疫引起了高水平的γ干扰素（IFN-gamma）产生，但当这些小鼠受到结核杆菌攻击时，我们没有观察到保护作用。为了利用CFP抗原的IFN-γ诱导能力，在本研究中，我们评估了基于CFP/CpG的初免-加强异源免疫来加强牛分枝杆菌BCG疫苗接种，以找到可以诱导保护的免疫方案。异源BCG-CFP/CpG免疫对实验性结核病提供了显著的保护，并且这种保护在感染的晚期持续，甚至比单一BCG免疫所赋予的保护更好。这种保护作用与高水平的抗原特异性IFN-γ和白细胞介素-17（IL-17）以及低水平的IL-4产生有关。当用CFP/CpG免疫的IL-4敲除小鼠显示出与BCG-CFP/CpG异源免疫引起的保护相似的一致性时，证实了IL-4的有害作用。这些发现表明，单剂量的CFP/CpG可以代表一种新的策略，以增强BCG疫苗接种所赋予的保护作用。此外，不同的免疫学参数，如IFN-γ和IL-17和严格调节的IL-4分泌，似乎有助于这种结核病疫苗的功效。
Culture filtrate proteins (CFP) are potential targets for tuberculosis vaccine development. We previously showed that despite the high level of gamma interferon (IFN-gamma) production elicited by homologous immunization with CFP plus CpG oligodeoxynucleotides (CFP/CpG), we did not observe protection when these mice were challenged with Mycobacterium tuberculosis. In order to use the IFN-gamma-inducing ability of CFP antigens, in this study we evaluated a prime-boost heterologous immunization based on CFP/CpG to boost Mycobacterium bovis BCG vaccination in order to find an immunization schedule that could induce protection. Heterologous BCG-CFP/CpG immunization provided significant protection against experimental tuberculosis, and this protection was sustained during the late phase of infection and was even better than that conferred by a single BCG immunization. The protection was associated with high levels of antigen-specific IFN-gamma and interleukin-17 (IL-17) and low IL-4 production. The deleterious role of IL-4 was confirmed when IL-4 knockout mice vaccinated with CFP/CpG showed consistent protection similar to that elicited by BCG-CFP/CpG heterologous immunization. These findings show that a single dose of CFP/CpG can represent a new strategy to boost the protection conferred by BCG vaccination. Moreover, different immunological parameters, such as IFN-gamma and IL-17 and tightly regulated IL-4 secretion, seem to contribute to the efficacy of this tuberculosis vaccine.