Tuberculosis Subunit Vaccination Provides Long-Term Protective Immunity Characterized by Multifunctional CD4 Memory T Cells
Tuberculosis Subunit Vaccination Provides Long-Term Protective Immunity Characterized by Multifunctional CD4 Memory T Cells
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DOI：
10.4049/jimmunol.0801592
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发表时间：
2009-06-15
影响因子：
4.4
通讯作者：
Andersen, Peter
中科院分区：
文献类型：
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作者：
Lindenstrom, Thomas;Agger, Else Marie;Andersen, Peter
对于一些仍然是全球健康问题的疾病，迫切需要能够促进长期细胞免疫的改进疫苗。在目前的研究中，我们证明了结核亚基疫苗Ag85B-ESAT-6/CAF01(其中ESAT-6是早期分泌的6 kDa的抗原靶标，CAF01是阳离子佐剂配方01)可以诱导非常强大的记忆CD4T细胞反应，并在接种后一年内保持在高水平。这种长期的、疫苗诱导的记忆反应可以在与卡介苗相当或更好的水平上抵御结核分枝杆菌的挑战。多色流式细胞仪检测显示，长寿命记忆T细胞几乎全部由肿瘤坏死因子-α+白介素2(+)和干扰素-γ+肿瘤坏死因子-α+白介素2(+)多功能T细胞组成。此外，免疫后1年分离的记忆细胞保持了很强的疫苗特异性增殖能力。卡介苗诱导的长期记忆包含较少的多功能T细胞，并且偏向于主要是肿瘤坏死因子-α+干扰素-γ(+)共表达亚群的效应细胞。Ag85B-ESAT-6/CAF01疫苗能非常有效地维持结核分枝杆菌感染后感染部位聚集的多功能CD4T细胞，而未免疫的动物主要表现为CD4效应T细胞。我们的数据表明，佐剂亚单位疫苗可以促进以高水平持续多功能T细胞为特征的长期保护性免疫反应，并且这种反应的质量和特征是感染后持续的。免疫学杂志，2009,182：8047-8055。
Improved vaccines capable of promoting long-term cellular immunity are urgently required for a number of diseases that remain global health problems. In the present study, we demonstrate that a tuberculosis subunit vaccine, Ag85B-ESAT-6/CAF01 (where ESAT-6 is early secreted antigenic target of 6 kDa and CAF01 is cationic adjuvant formulation 0l), induces very robust memory CD4 T cell responses that are maintained at high levels for >1 year postvaccination. This long-term, vaccine-induced memory response protects against a challenge with Mycobacterium tuberculosis at levels that are comparable to or better than those of bacillus Calmette-Guerin. Characterization of the CD4 memory T cells by multicolor flow cytometry demonstrated that the long-lived memory population consisted almost exclusively of TNF-alpha+IL-2(+) and IFN-gamma+TNF-alpha+IL-2(+) multifunctional T cells. In addition, memory cells isolated >1 year postvaccination maintained a strong, vaccine-specific proliferative potential. Long-term memory induced by the BCG vaccine contained fewer multifunctional T cells and was biased toward effector cells mainly of the TNF-alpha+IFN-gamma(+)-coexpressing subset. Ag85B-ESAT-6/CAF01 vaccination very efficiently sustained multifunctional CD4 T cells that accumulated at the site of infection after M. tuberculosis challenge, whereas the response in unvaccinated animals was characterized by CD4 effector T cells. Our data demonstrate that adjuvanted subunit vaccines can promote long-term protective immune responses characterized by high levels of persisting multifunctional T cells and that the quality and profile of this response is sustained postinfection. The Journal of Immunology, 2009, 182: 8047-8055.