Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Tuberculosis Centre, London School of Hygiene and Tropical Medicine, London, UK.
Sci Rep. 2019 Mar 19;9(1):4842. doi: 10.1038/s41598-019-41008-4.
Tuberculosis (TB) is a leading infectious cause of death globally. Drug treatment and vaccination, in particular with Bacillus Calmette-Guérin (BCG), remain the main strategies to control TB. With the emergence of drug resistance, it has been proposed that a combination of TB vaccination with pharmacological treatment may provide a greater therapeutic value. We implemented an ex vivo mycobacterial growth inhibition assay (MGIA) to discriminate vaccine responses in historically BCG-vaccinated human volunteers and to assess the contribution of vaccine-mediated immune response towards the killing effect of mycobacteria in the presence of the antibiotics isoniazid (INH) and rifampicin (RIF), in an attempt to develop the assay as a screening tool for therapeutic TB vaccines. BCG vaccination significantly enhanced the ability of INH to control mycobacterial growth ex vivo. The BCG-vaccinated group displayed a higher production of IFN-γ and IP-10 when peripheral blood mononuclear cells (PBMC) were co-cultured with INH, with a similar trend during co-culture with RIF. A higher frequency of IFN-γ and TNF-α CD3 CD4 CD8 cells was observed, suggesting the contribution of Natural Killer (NK) cells in the combined effect between BCG vaccination and INH. Taken together, our data indicate the efficacy of INH can be augmented following historical BCG vaccination, which support findings from previous observational and animal studies.
结核病（TB）是全球主要的传染病死因之一。药物治疗和疫苗接种，特别是使用卡介苗（BCG），仍然是控制结核病的主要策略。随着耐药性的出现，有人提出将结核病疫苗接种与药物治疗相结合可能提供更大的治疗价值。我们实施了体外分枝杆菌生长抑制试验（MGIA），以区分历史上接种过卡介苗的人类志愿者的疫苗反应，并评估疫苗介导的免疫反应对异烟肼（INH）和利福平（RIF）存在时抗结核分枝杆菌杀伤作用的贡献，试图开发该检测作为治疗性结核疫苗的筛选工具。BCG 疫苗接种显著增强了 INH 控制分枝杆菌体外生长的能力。当外周血单核细胞（PBMC）与 INH 共培养时，BCG 接种组产生了更高水平的 IFN-γ和 IP-10，与 RIF 共培养时也呈现出类似的趋势。观察到 IFN-γ和 TNF-α CD3 CD4 CD8 细胞的频率更高，表明 NK 细胞在 BCG 接种和 INH 联合作用中的贡献。总之，我们的数据表明，BCG 疫苗接种后 INH 的疗效可以增强，这支持了之前观察性和动物研究的发现。
