近日，美国国立卫生研究院Robert A. Seder及其团队的最新研究指出，静脉注射卡介苗（BCG）可在猕猴中预防结核病。2020年1月1日，国际学术期刊《自然》在线发表了这一研究成果。
研究人员发现，静脉注射BCG可以显著改变非人类灵长类动物（猕猴）中结核分枝杆菌（Mtb）的感染结果。与皮内或气雾剂递送相比，静脉内免疫在血液、脾脏、支气管肺泡灌洗和肺淋巴结中诱导了更多的抗原反应性CD4和CD8 T细胞反应。此外，静脉免疫在所有肺实质组织中诱导了高频率的抗原反应性T细胞。卡介苗接种六个月后，猕猴接受了有毒的Mtb感染。值得注意的是，接受了BCG静脉注射的十只猕猴中有九只受到了高度保护，并且六只猕猴显示出没有可检测的感染水平，这由正电子发射断层扫描－计算机断层摄影成像、分枝杆菌生长、病理学和肉芽肿的形成判断所确定。静脉BCG可预防或大大限制了高度易感恒河猴的Mtb感染，这一发现对疫苗的递送和临床开发具有重要意义，并为定义免疫相关性和疫苗引发的抗结核保护机制提供了模型。
研究人员表示，Mtb是全世界感染死亡的主要原因。唯一可用的疫苗BCG皮内注射，对肺结核（死亡率和疾病传播的主要原因）具有不确定的疗效。
附：英文原文
Title: Prevention of tuberculosis in macaques after intravenous BCG immunization
Author: Patricia A. Darrah, Joseph J. Zeppa, Pauline Maiello, Joshua A. Hackney, Marc H. Wadsworth, Travis K. Hughes, Supriya Pokkali, Phillip A. Swanson, Nicole L. Grant, Mark A. Rodgers, Megha Kamath, Chelsea M. Causgrove, Dominick J. Laddy, Aurelio Bonavia, Danilo Casimiro, Philana Ling Lin, Edwin Klein, Alexander G. White, Charles A. Scanga, Alex K. Shalek, Mario Roederer, JoAnne L. Flynn, Robert A. Seder
Issue&Volume: 2020-01-01
Abstract: Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide1. The only available vaccine, BCG (Bacillus Calmette–Guérin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission1,2. Here we show that intravenous administration of BCG profoundly alters the protective outcome of Mtb challenge in non-human primates (Macaca mulatta). Compared with intradermal or aerosol delivery, intravenous immunization induced substantially more antigen-responsive CD4 and CD8 T cell responses in blood, spleen, bronchoalveolar lavage and lung lymph nodes. Moreover, intravenous immunization induced a high frequency of antigen-responsive T cells across all lung parenchymal tissues. Six months after BCG vaccination, macaques were challenged with virulent Mtb. Notably, nine out of ten macaques that received intravenous BCG vaccination were highly protected, with six macaques showing no detectable levels of infection, as determined by positron emission tomography–computed tomography imaging, mycobacterial growth, pathology and granuloma formation. The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis.
DOI: 10.1038/s41586-019-1817-8
Source: https://www.nature.com/articles/s41586-019-1817-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
