TB Centre, London School of Hygiene & Tropical Medicine, London, UK.
Semin Immunol. 2018 Oct;39:81-87. doi: 10.1016/j.smim.2018.10.001. Epub 2018 Oct 10.
Tuberculosis (TB) is the leading cause of death due to a single infectious disease and an effective vaccine would substantially accelerate global efforts to control TB. An immune correlate of protection (CoP) from TB disease could aid vaccine optimization and licensure. This paper summarises opportunities for identifying CoP and highlights results from correlates of risk studies. Although we don't have CoP, there are ongoing efficacy trials with both disease and infection endpoints which provide opportunities for such an analysis. Transcriptomics has successfully identified robust CoR, with transcripts found in the Type I IFN pathway. Correlates of lower risk include BCG antigen specific IFN-γ and natural killer cells. Collating evidence from multiple studies using a range of systems approaches supports a role for IFN-γ in protection from TB disease. In addition, the cells that express the IFN-γ receptor are also important in protective immunity. Protection is a culmination not only of the amount of IFN-γ produced by T cells and NK cells but by the ability of IFN-γ receptor expressing monocytes to respond to IFN-γ. To better understand IFN-γ as a correlate we need to understand host-factors such as age, sex, co-infection, nutritional status and stress which may alter or impair the ability of cells to respond to IFN-γ. These studies highlight recent advances in our understanding of the immune mechanisms of TB disease risk and show the importance of whole systems approaches to correlates of risk analysis. CoP may be useful tools for specific vaccine products in specific populations, but a well-designed CoR analysis can identify novel immune mechanisms and provide insights critical for the development of new and better TB vaccines.
结核病（TB）是单一传染病导致死亡的主要原因，如果有一种有效的疫苗，将极大地促进全球控制结核病的努力。结核病疾病的免疫相关保护指标（CoP）可以帮助疫苗优化和许可。本文总结了确定 CoP 的机会，并强调了风险研究相关结果。虽然我们还没有 CoP，但有针对疾病和感染终点的正在进行的疗效试验，这为这种分析提供了机会。转录组学已成功识别出强有力的 CoR，其中包括 I 型 IFN 途径中的转录本。较低风险的相关因素包括 BCG 抗原特异性 IFN-γ和自然杀伤细胞。综合使用多种系统方法的多项研究证据支持 IFN-γ在预防结核病中的作用。此外，表达 IFN-γ受体的细胞在保护性免疫中也很重要。保护不仅是 T 细胞和 NK 细胞产生的 IFN-γ量的结果，也是表达 IFN-γ受体的单核细胞对 IFN-γ作出反应的能力的结果。为了更好地理解 IFN-γ作为一种相关因素，我们需要了解宿主因素，如年龄、性别、合并感染、营养状况和压力，这些因素可能会改变或损害细胞对 IFN-γ的反应能力。这些研究强调了我们对结核病疾病风险免疫机制的理解的最新进展，并显示了全系统方法对风险分析相关因素的重要性。CoP 可能对特定人群的特定疫苗产品有用，但精心设计的 CoR 分析可以识别新的免疫机制，并为开发新的和更好的结核病疫苗提供关键见解。
