Investigating the Induction of Vaccine-Induced Th17 and Regulatory T Cells in Healthy, Mycobacterium bovis BCG-Immunized Adults Vaccinated with a New Tuberculosis Vaccine, MVA85A

Investigating the Induction of Vaccine-Induced Th17 and Regulatory T Cells in Healthy, Mycobacterium bovis BCG-Immunized Adults Vaccinated with a New Tuberculosis Vaccine, MVA85A
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DOI:
10.1128/cvi.00047-10
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发表时间:
2010-07-01
影响因子:
--
通讯作者:
Fletcher, Helen A.
Fletcher, Helen A.
中科院分区:
生物3区
文献类型:
--
作者:
de Cassan, Simone C.;Pathan, Ansar A.;Fletcher, Helen A.

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结核病仍然是对全球健康的威胁。虽然诊断和治疗方面的进展对遏制这一流行病至关重要,但很可能只有通过接种疫苗才能消除这一疾病。疫苗诱导的对结核分枝杆菌的保护作用至少部分依赖于强大的Th1应答,但对结核病疫苗诱导其他可能影响疫苗效力的t细胞亚群的能力知之甚少。白细胞介素- 17a (IL-17A)是一种由Th17细胞产生的促炎细胞因子,与免疫病理和预防传染病有关。接种MVA85A(一种旨在增强对结核分枝杆菌免疫应答的病毒载体疫苗)后,在健康志愿者的外周血中诱导产生抗原特异性il - 17a的T细胞。这些T细胞比γ干扰素(ifn - γ)分泌T细胞被检测到的时间要晚,而且强度低。预先存在的对分枝杆菌抗原的免疫应答与外周血中较高的CD4(+) CD25(hi) CD39(+) t细胞水平和免疫后产生IL-17A的能力降低有关。这些数据强调了疫苗接种诱导的效应免疫反应和调节性免疫反应的复杂平衡,以及预先存在的对分枝杆菌抗原的免疫可能影响疫苗诱导的t细胞亚群的组成。
Tuberculosis (TB) remains a threat to global health. While advances in diagnostics and treatment are crucial to the containment of the epidemic, it is likely that elimination of the disease can only be achieved through vaccination. Vaccine-induced protection from Mycobacterium tuberculosis is dependent, at least in part, on a robust Th1 response, yet little is known of the ability of TB vaccines to induce other T-cell subsets which may influence vaccine efficacy. Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by Th17 cells which has been associated with both immune pathology and protection against infectious disease. Following vaccination with MVA85A, a viral vector vaccine aimed at enhancing immune responses to M. tuberculosis, antigen-specific IL-17A-producing T cells were induced in the peripheral blood of healthy volunteers. These T cells are detected later than gamma interferon (IFN-gamma)-secreting T cells and are of a low magnitude. Preexisting immune responses to mycobacterial antigens were associated with higher CD4(+) CD25(hi) CD39(+) T-cell levels in the periphery and a reduced capacity to produce IL-17A following immunization. These data highlight the intricate balance of effector and regulatory immune responses induced by vaccination and that preexisting immunity to mycobacterial antigens may affect the composition of vaccine-induced T-cell subsets.