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结核病控制的最新进展:疫苗和生物标志物。

Recent advances towards tuberculosis control: vaccines and biomarkers.

机构信息

Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.

出版信息

J Intern Med. 2014 May;275(5):467-80. doi: 10.1111/joim.12212.

Abstract

Of all infectious diseases, tuberculosis (TB) remains one of the most important causes of morbidity and mortality. Recent advances in understanding the biology of Mycobacterium tuberculosis (Mtb) infection and the immune response of the infected host have led to the development of several new vaccines, a number of which are already undergoing clinical trials. These include pre-exposure prime vaccines, which could replace bacille Calmette-Guérin (BCG), and pre-exposure booster vaccines given in addition to BCG. Infants are the target population of these two types of vaccines. In addition, several postexposure vaccines given during adolescence or adult life, in addition to BCG as a priming vaccine during infancy, are undergoing clinical testing. Therapeutic vaccines are currently being assessed for their potential to cure active TB as an adjunct to chemotherapy. BCG replacement vaccines are viable recombinant BCG or double-deletion mutants of Mtb. All booster vaccines are composed of one or several antigens, either expressed by viral vectors or formulated with adjuvants. Therapeutic vaccines are killed mycobacterial preparations. Finally, multivariate biomarkers and biosignatures are being generated from high-throughput data with the aim of providing better diagnostic tools to specifically determine TB progression. Here, we provide a technical overview of these recent developments as well of the relevant computational approaches and highlight the obstacles that still need to be overcome.

摘要

在所有传染病中,结核病(TB)仍然是发病率和死亡率的最重要原因之一。最近对结核分枝杆菌(Mtb)感染的生物学和受感染宿主的免疫反应的理解的进展,导致了几种新疫苗的开发,其中一些已经在进行临床试验。这些疫苗包括暴露前初级疫苗,它可以替代卡介苗(BCG),以及暴露前加强疫苗,除了 BCG 之外还可以使用。这两种类型的疫苗的目标人群是婴儿。此外,正在进行临床试验,在青少年或成年期使用几种暴露后疫苗,除了 BCG 作为婴儿期的初级疫苗。治疗性疫苗目前正在评估其作为辅助化疗治愈活动性结核病的潜力。BCG 替代疫苗是可行的重组 BCG 或 Mtb 的双重缺失突变体。所有加强疫苗都由一种或多种抗原组成,这些抗原可以由病毒载体表达,也可以与佐剂一起配制。治疗性疫苗是死菌的制备物。最后,正在从高通量数据中生成多变量生物标志物和生物特征,以提供更好的诊断工具,专门确定结核病的进展。在这里,我们提供了这些最新进展的技术概述以及相关的计算方法,并强调了仍然需要克服的障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129c/4238842/9dedb238eeea/joim0275-0467-f1.jpg

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