Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV-BH19), Rue du Bugnon, CH-1011 Lausanne, Switzerland.
Tuberculosis (Edinb). 2013 Mar;93(2):179-88. doi: 10.1016/j.tube.2012.10.011. Epub 2012 Dec 5.
Prevention of tuberculosis (TB) through vaccination would substantially reduce the global TB burden. Mtb72F/AS02 is a candidate TB vaccine shown to be immunogenic and well tolerated in PPD-negative adults. We evaluated the safety and immunogenicity of Mtb72F/AS02 in Mycobacterium-primed adults (BCG-vaccinated, or infected adults who had received post-exposure chemoprophylaxis or treatment for pulmonary TB disease). In this observer-blind controlled trial, 20 BCG-vaccinated adults and 18 adults previously infected with Mycobacterium tuberculosis (Mtb), were randomized 3:1 to receive three doses of Mtb72F/AS02 or AS02 at one-month intervals, and followed for 6 months post third vaccination. Mtb72F/AS02 was well tolerated in BCG-vaccinated adults, and tended to be more reactogenic in Mtb-infected adults. Adverse events were mainly self-limiting, resolving without sequelae. No serious adverse events were reported. The adverse events in Mtb72F/AS02 vaccinees were not clearly associated with vaccine-induced responses (as assessed by proinflammatory cytokines, total IgE and C-reactive protein levels). No Th2 T-cell responses, or vaccine-induced T-cell responses to Mtb antigens (CFP-10/PPD/ESAT-6) were detected by ICS. In both cohorts, Mtb72F/AS02 induced persistent polyfunctional Mtb72F-specific CD4(+) T-cell responses and anti-Mtb72F humoral responses. IFN-γ was detectable in serum one day post each vaccination. Further evaluation of the candidate vaccine, Mtb72F/AS02, is warranted.
ClinicalTrials.gov identifier: NCT00146744.
通过疫苗接种预防结核病（TB）将大大降低全球结核病负担。Mtb72F/AS02 是一种候选结核病疫苗，已证明在 PPD 阴性成人中具有免疫原性和良好的耐受性。我们评估了 Mtb72F/AS02 在结核分枝杆菌（BCG 疫苗接种者或曾接受过接触后化学预防或治疗肺结核疾病的感染者）启动的成年人中的安全性和免疫原性。在这项观察者盲法对照试验中，20 名 BCG 疫苗接种者和 18 名先前感染结核分枝杆菌（Mtb）的成年人按 3:1 随机接受 Mtb72F/AS02 或 AS02 三剂，每剂间隔一个月，并在第三次接种后随访 6 个月。Mtb72F/AS02 在 BCG 疫苗接种者中耐受性良好，在 Mtb 感染者中反应性更强。不良事件主要为自限性，无后遗症消退。未报告严重不良事件。Mtb72F/AS02 疫苗接种者的不良事件与疫苗诱导的反应（通过促炎细胞因子、总 IgE 和 C 反应蛋白水平评估）无明显关联。未通过 ICS 检测到 Th2 T 细胞反应或疫苗诱导的 Mtb 抗原（CFP-10/PPD/ESAT-6）的 T 细胞反应。在两个队列中，Mtb72F/AS02 均诱导持久的多能 Mtb72F 特异性 CD4(+) T 细胞反应和抗 Mtb72F 体液反应。每次接种后一天，血清中均可检测到 IFN-γ。需要进一步评估候选疫苗 Mtb72F/AS02。
ClinicalTrials.gov 标识符：NCT00146744。
