From the, La Jolla Institute for Immunology, La Jolla, CA, USA.
Department of Medicine, University of California San Diego, USA.
J Intern Med. 2020 Dec;288(6):651-660. doi: 10.1111/joim.13191. Epub 2020 Nov 19.
In recent years, the century-old Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has been re-evaluated for its capacity to stem the global tide of TB. There is increasing evidence that the efficacy of BCG can be improved by the modified administration methods and schedules. Here, we first discuss recent approaches of vaccine administration, revaccination or boosting that have been used to try to improve the efficacy of BCG against TB. We then dive deeper into studies investigating the immune correlates of protection and describe studies that have investigated BCG-specific T-cell responses and the influence of environmental exposures. These studies all highlight that there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity, which has been surprisingly understudied. We argue that several critical gaps in knowledge exist and must be addressed by future research to rationally improve the efficacy of BCG, including comprehensive, proteome-wide understanding of the epitopes derived from BCG recognized by BCG-vaccinated individuals, the phenotype of responding antigen-specific T cells and how previous exposure to environmental mycobacteria affect these parameters and thus influence vaccine efficacy. The development of modern techniques allows us to answer some of these questions to better understand how BCG works in terms of both protection against TB and the immune response that it triggers.
近年来，用于预防结核病（TB）的百年牛型分枝杆菌卡介苗（BCG）疫苗在防治全球结核病流行方面的作用重新受到评估。越来越多的证据表明，通过改变接种方法和方案可以提高 BCG 的效力。在这里，我们首先讨论了最近用于尝试提高 BCG 对结核病疗效的疫苗接种管理、再接种或加强接种方法。然后，我们更深入地研究了免疫保护相关因素，并描述了研究 BCG 特异性 T 细胞反应和环境暴露影响的研究。这些研究都强调，人们对 BCG 诱导的免疫反应，无论是表型还是特异性，仍有很多需要了解，而这方面的研究出人意料地很少。我们认为，未来的研究必须解决几个关键的知识空白，以合理地提高 BCG 的功效，包括全面、全蛋白质组水平了解 BCG 疫苗接种个体识别的 BCG 衍生表位、应答抗原特异性 T 细胞的表型以及先前接触环境分枝杆菌如何影响这些参数，从而影响疫苗功效。现代技术的发展使我们能够回答其中的一些问题，从而更好地了解 BCG 在预防结核病和引发的免疫反应方面的作用。
