Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Infect Immun. 2023 Jul 18;91(7):e0016823. doi: 10.1128/iai.00168-23. Epub 2023 Jun 20.
Tuberculosis is still the leading cause of death globally from any infectious disease, despite the widespread use of the live attenuated vaccine Bacille Calmette Guerin (BCG). While BCG has some efficacy against disseminated TB disease in children, protection wanes into adulthood resulting in over 1.8 million TB deaths per year. This has led to efforts to develop novel vaccine candidates that either replace or boost BCG, as well as to test novel delivery mechanisms to enhance BCG's efficacy. Traditional BCG vaccination is performed as an intradermal (ID) injection but delivering BCG by an alternate route may enhance the depth and breadth of protection. Previously, we demonstrated that phenotypically and genotypically disparate Diversity Outbred (DO) mice have heterogenous responses to M. tuberculosis challenge following intradermal BCG vaccination. Here, we utilize DO mice to examine BCG-induced protection when BCG is delivered systemically via intravenous (IV) administration. We find that DO mice vaccinated with IV BCG had a greater distribution of BCG throughout their organs compared to ID-vaccinated animals. However, compared to ID-vaccinated mice, M. tuberculosis burdens in lungs and spleens were not significantly reduced in animals vaccinated with BCG IV, nor was lung inflammation significantly altered. Nonetheless, DO mice that received BCG IV had increased survival over those vaccinated by the traditional ID route. Thus, our results suggest that delivering BCG by the alternate IV route enhances protection as detected in this diverse small animal model.
结核病仍然是全球任何传染病导致死亡的主要原因，尽管广泛使用了减毒活疫苗卡介苗（BCG）。虽然 BCG 对儿童播散性结核病有一定疗效，但随着年龄的增长，保护作用逐渐减弱，导致每年有超过 180 万人死于结核病。这导致人们努力开发新型疫苗候选物，以替代或增强 BCG 的作用，并测试新的输送机制来增强 BCG 的疗效。传统的 BCG 接种是通过皮内（ID）注射进行的，但通过替代途径接种 BCG 可能会增强保护的深度和广度。以前，我们证明表型和基因型不同的多样性远交（DO）小鼠在接受皮内 BCG 接种后对结核分枝杆菌的挑战有不同的反应。在这里，我们利用 DO 小鼠来研究通过静脉内（IV）给药全身接种 BCG 时 BCG 诱导的保护作用。我们发现，与 ID 接种的动物相比，通过 IV 接种 BCG 的 DO 小鼠其器官中 BCG 的分布更为广泛。然而，与 ID 接种的小鼠相比，BCG IV 接种的动物肺部和脾脏中的结核分枝杆菌负荷并没有明显减少，肺部炎症也没有明显改变。尽管如此，接受 BCG IV 接种的 DO 小鼠的存活率高于通过传统 ID 途径接种的小鼠。因此，我们的结果表明，通过替代的 IV 途径接种 BCG 可以增强在这种多样化的小型动物模型中检测到的保护作用。
