DAR-901 和卡介苗诱导的分枝杆菌免疫力

Getahun Abate, Krystal A Meza, Chase Colbert, Christopher S Eickhoff
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摘要

在欧洲和北美,肺非结核分枝杆菌(NTM)的发病率正在上升。大多数肺非结核分枝杆菌由复合分枝杆菌(MAC)引起。肺部 MAC 的治疗效果并不理想,失败率在 30% 到 40% 之间,因此需要开发新的疫苗。在本研究中,我们测试了两种全细胞疫苗--DAR-901(热杀M. obuense)和卡介苗(减毒M. bovis活疫苗)--诱导MAC交叉反应免疫的能力,首先免疫BALB/c小鼠,然后用活MAC刺激脾细胞过夜后进行IFN-gamma ELISPOT检测。为了研究这些疫苗对 MAC 感染的保护能力,给 BALB/c 小鼠接种了 DAR-901(皮内)或卡介苗(皮下或鼻内),4 周后用气雾化 MAC 进行挑战。一些接种卡介苗的小鼠通过灌胃接受了克拉霉素治疗。感染 4 周后,对免疫小鼠和未接种对照组的肺部 CFU 进行量化。我们的研究结果表明:i)DAR-901 能诱导 MAC 交叉反应免疫,MAC 交叉反应免疫水平与卡介苗诱导的免疫水平相似;ii)DAR-901 和卡介苗都能抵御气溶胶 MAC;iii)卡介苗粘膜接种能为 MAC 挑战提供最佳保护;iv)卡介苗接种不会干扰克拉霉素的抗 MAC 活性。
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Immunity against Mycobacterium avium induced by DAR-901 and BCG
The prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing in Europe and North America. Most pulmonary NTM are caused by Mycobacterium avium complex (MAC). The treatment of pulmonary MAC is suboptimal with failure rates ranging from 30% to 40% and there is a need to develop new vaccines. In this study, we tested the ability of two whole cell vaccines, DAR-901 (heat killed M. obuense) and BCG (live attenuated M. bovis), to induce MAC cross-reactive immunity by first immunizing BALB/c mice and then performing IFN-gamma ELISPOT assay after overnight stimulation of splenocytes with live MAC. To study the ability of these vaccines to protect against MAC infection, BALB/c mice were vaccinated with DAR-901 (intradermal) or BCG (subcutaneous or intranasal) and challenged with aerosolized MAC 4 weeks later. Some mice vaccinated with BCG were treated with clarithromycin via gavage. Lung CFU in immunized mice and unvaccinated controls were quantified 4 weeks after infection. Our results showed that i) DAR-901 induced cross-reactive immunity to MAC and the level of MAC cross-reactive immunity was similar to the level of immunity induced by BCG, ii) DAR-901 and BCG protect against aerosol MAC, iii) mucosal BCG vaccination provided the best protection against MAC challenge, and iv) BCG vaccination did not interfere with anti-MAC activities of clarithromycin.
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