South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine and School of Child and Adolescent Health,University of Cape Town, UCT Health Sciences, Anzio Road, Observatory 7925, Cape Town, South Africa.
Am J Respir Crit Care Med. 2010 Jun 15;181(12):1407-17. doi: 10.1164/rccm.200910-1484OC. Epub 2010 Feb 18.
AERAS-402 is a novel tuberculosis vaccine designed to boost immunity primed by bacillus Calmette-Guérin (BCG), the only licensed vaccine.
We investigated the safety and immunogenicity of AERAS-402 in healthy Mycobacterium tuberculosis-uninfected BCG-vaccinated adults from a tuberculosis-endemic region of South Africa.
Escalating doses of AERAS-402 vaccine were administered intramuscularly to each of three groups of healthy South African BCG-vaccinated adults, and a fourth group received two injections of the maximal dose. Participants were monitored for 6 months, with all adverse effects documented. Vaccine-induced CD4(+) and CD8(+) T-cell immunity was characterized by an intracellular cytokine staining assay of whole blood and peripheral blood mononuclear cells.
AERAS-402 was well tolerated, and no vaccine-related serious adverse events were recorded. The vaccine induced a robust CD4(+) T-cell response dominated by cells coexpressing IFN-gamma, tumor necrosis factor-alpha, and IL-2 ("polyfunctional" cells). AERAS-402 also induced a potent CD8(+) T-cell response, characterized by cells expressing IFN-gamma and/or tumor necrosis factor-alpha, which persisted for the duration of the study.
Vaccination with AERAS-402 is safe and immunogenic in healthy adults. The immunity induced by the vaccine appears promising: polyfunctional T cells are thought to be important for protection against intracellular pathogens such as Mycobacterium tuberculosis, and evidence is accumulating that CD8(+) T cells are also important. AERAS-402 induced a robust and durable CD8(+) T-cell response, which appears extremely promising. Clinical trial registered with www.sanctr.gov.za (NHREC no. 1381).
AERAS-402 是一种新型结核疫苗，旨在增强卡介苗（BCG）引发的免疫，BCG 是唯一获得许可的疫苗。
我们研究了 AERAS-402 在南非结核病流行地区未感染结核分枝杆菌且已接种 BCG 的健康成年人中的安全性和免疫原性。
将递增剂量的 AERAS-402 疫苗肌肉注射到三组健康的南非 BCG 接种成年人中，第四组接受两剂最大剂量。监测参与者 6 个月，记录所有不良反应。通过全血和外周血单个核细胞的细胞内细胞因子染色测定来描述疫苗诱导的 CD4(+)和 CD8(+)T 细胞免疫。
AERAS-402 耐受性良好，未记录到与疫苗相关的严重不良事件。疫苗诱导了以共表达 IFN-γ、肿瘤坏死因子-α和 IL-2 的细胞（“多功能”细胞）为主的强烈的 CD4(+)T 细胞应答。AERAS-402 还诱导了强有力的 CD8(+)T 细胞应答，其特征是表达 IFN-γ和/或肿瘤坏死因子-α的细胞，该应答在研究期间持续存在。
AERAS-402 在健康成年人中安全且具有免疫原性。疫苗诱导的免疫似乎很有希望：多功能 T 细胞被认为对保护细胞内病原体（如结核分枝杆菌）很重要，并且有证据表明 CD8(+)T 细胞也很重要。AERAS-402 诱导了强烈且持久的 CD8(+)T 细胞应答，这非常有前景。临床试验在 www.sanctr.gov.za（NHREC 编号 1381）注册。
