South African Tuberculosis Vaccine Initiative and School of Child and Adolescent Health, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Eur J Immunol. 2013 Sep;43(9):2409-20. doi: 10.1002/eji.201343454. Epub 2013 Jul 8.
Heterologous prime-boost strategies hold promise for vaccination against tuberculosis. However, the T-cell characteristics required for protection are not known. We proposed that boost vaccines should induce long-lived functional and phenotypic changes to T cells primed by Bacille Calmette Guerin (BCG) and/or natural exposure to mycobacteria. We characterized changes among specific CD4(+) T cells after vaccination with the MVA85A vaccine in adults, adolescents, and children. CD4(+) T cells identified with Ag85A peptide-bearing HLA class II tetramers were characterized by flow cytometry. We also measured proliferative potential and cytokine expression of Ag85A-specific CD4(+) T cells. During the effector phase, MVA85A-induced specific CD4(+) T cells coexpressed IFN-γ and IL-2, skin homing integrins, and the activation marker CD38. This was followed by contraction and a transition to predominantly IL-2-expressing, CD45RA(-) CCR7(+) CD27(+) or CD45RA(+) CCR7(+) CD27(+) specific CD4(+) T cells. These surface phenotypes were similar to Ag85A-specific T cells prior to MVA85A. However, functional differences were observed postvaccination: specific proliferative capacity was markedly higher after 6-12 months than before vaccination. Our data suggest that MVA85A vaccination may modulate Ag85A-specific CD4(+) T-cell function, resulting in greater recall potential. Importantly, surface phenotypes commonly used as proxies for memory T-cell function did not associate with functional effects of vaccination.
异源初免-加强策略有望用于结核病疫苗接种。然而，保护所需要的 T 细胞特征尚不清楚。我们提出，加强疫苗应该诱导卡介苗（BCG）和/或自然暴露于分枝杆菌所引发的 T 细胞产生长期的功能和表型变化。我们在成年人、青少年和儿童中研究了 MVA85A 疫苗接种后特定 CD4(+)T 细胞的变化。用携带 Ag85A 肽的 HLA Ⅱ类四聚体鉴定 CD4(+)T 细胞，并用流式细胞术进行分析。我们还测量了 Ag85A 特异性 CD4(+)T 细胞的增殖潜力和细胞因子表达。在效应期，MVA85A 诱导的特异性 CD4(+)T 细胞共表达 IFN-γ和 IL-2、皮肤归巢整合素和激活标志物 CD38。随后发生收缩，并向主要表达 IL-2、CD45RA(-)CCR7(+)CD27(+)或 CD45RA(+)CCR7(+)CD27(+)特异性 CD4(+)T 细胞的状态转变。这些表面表型与 MVA85A 之前的 Ag85A 特异性 T 细胞相似。然而，接种疫苗后观察到功能差异：接种后 6-12 个月特异性增殖能力明显高于接种前。我们的数据表明，MVA85A 疫苗接种可能调节 Ag85A 特异性 CD4(+)T 细胞功能，从而提高记忆潜能。重要的是，作为记忆 T 细胞功能替代指标的表面表型与疫苗接种的功能效应无关。
