Repurposing mucosal delivery devices for live attenuated tuberculosis vaccines.
Repurposing mucosal delivery devices for live attenuated tuberculosis vaccines.
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DOI：
10.3389/fimmu.2023.1159084
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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结核病(TB)仍然是全球最致命的传染病之一。世界卫生组织批准的唯一结核病疫苗是卡介苗(BCG)，它可以保护儿童免受严重和播散性结核病的侵袭，但对成年人的肺结核病提供的保护有限。尽管已经开发了几种候选疫苗来预防结核病，并正在进行临床前和临床测试，但卡介苗仍然是黄金标准。目前，卡介苗是作为皮内注射使用的，特别是在结核病流行国家。然而，来自实验动物和人体研究的越来越多的证据表明，将卡介苗直接输送到肺部可以增强免疫反应，并更好地预防结核病。使用手持递送设备的吸入疗法用于某些疾病，并允许将药物或疫苗直接递送到人类呼吸道。目前尚不清楚这种递送方式是否也适用于卡介苗等减毒活细菌疫苗或其他候选结核病疫苗。在这里，我们讨论如何将用于流感疫苗的粘膜雾化装置(MAD)注射器和用于慢性阻塞性肺疾病治疗的Respimat®软雾™吸入器这两种现有的吸入设备重新用于粘膜递送减毒活结核疫苗。我们还概述了挑战和悬而未决的研究问题，这些挑战和悬而未决的研究问题将需要进一步调查，以确保具有成本效益并可供低收入和中等收入结核病流行国家使用的呼吸输送装置的有效性。
Tuberculosis (TB) remains one of the most lethal infectious diseases globally. The only TB vaccine approved by the World Health Organization, Bacille Calmette-Guérin (BCG), protects children against severe and disseminated TB but provides limited protection against pulmonary TB in adults. Although several vaccine candidates have been developed to prevent TB and are undergoing preclinical and clinical testing, BCG remains the gold standard. Currently, BCG is administered as an intradermal injection, particularly in TB endemic countries. However, mounting evidence from experimental animal and human studies indicates that delivering BCG directly into the lungs provides enhanced immune responses and greater protection against TB. Inhalation therapy using handheld delivery devices is used for some diseases and allows the delivery of drugs or vaccines directly into the human respiratory tract. Whether this mode of delivery could also be applicable for live attenuated bacterial vaccines such as BCG or other TB vaccine candidates remains unknown. Here we discuss how two existing inhalation devices, the mucosal atomization device (MAD) syringe, used for influenza vaccines, and the Respimat® Soft Mist™ inhaler, used for chronic obstructive pulmonary disease (COPD) therapy, could be repurposed for mucosal delivery of live attenuated TB vaccines. We also outline the challenges and outstanding research questions that will require further investigations to ensure usefulness of respiratory delivery devices that are cost-effective and accessible to lower- and middle-income TB endemic countries.