Boggiano Cesar, Eichelberg Katrin, Ramachandra Lakshmi, Shea Jaqueline, Ramakrishnan Lalita, Behar Samuel, Ernst Joel D, Porcelli Steven A, Maeurer Markus, Kornfeld Hardy
Division of AIDS/NIAID/NIH, 5601 Fishers Lane, Rm: 9D10B, MSC: 9829, Rockville, MD 20852, USA.
Division of Microbiology and Infectious Diseases/NIAID/NIH, Rockville, MD, USA.
Vaccine. 2017 Jun 14;35(27):3433-3440. doi: 10.1016/j.vaccine.2017.04.007. Epub 2017 May 2.
Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission.
结核病是全球传染病致死的主要原因,在艾滋病毒感染者中尤为如此。结核病疫苗的设计与研发一直聚焦于改进卡介苗(BCG)以及评估重组和病毒载体表达的结核分枝杆菌(Mtb)蛋白,以增强卡介苗引发的免疫力,但这些方法相较于卡介苗在预防感染或疾病方面的有限效果,尚未带来显著改善。2016年3月7日至8日,美国国立过敏与传染病研究所(NIAID)召开了一次关于“Mtb免疫逃逸对保护性免疫的影响:对结核病疫苗设计的启示”的研讨会,目的是确定可通过新研究方法靶向的免疫机制,为结核病预防的疫苗设计和免疫治疗干预提供依据。该研讨会探讨了早期感染事件、Mtb进化对适应性免疫反应的发展和维持的影响,以及影响预防和进展为活动性疾病的因素。讨论并确定了振兴和加速结核病疫苗设计的科学差距和研究领域。这些包括对疾病不同阶段肺部固有免疫和Mtb特异性适应性免疫反应的全面评估;确定B细胞和抗体(Abs)在Mtb感染过程中的作用;开发更好的检测方法来测量接触、感染、潜伏和治疗后Mtb的负担,以及改进当前动物模型以研究Mtb免疫原性、结核病疾病和传播的方法。