South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and School of Child and Adolescent Health, University of Cape Town, South Africa.
J Infect Dis. 2011 Jun 15;203(12):1832-43. doi: 10.1093/infdis/jir195.
BCG, the only licensed tuberculosis vaccine, affords poor protection against lung tuberculosis in infants and children. A new tuberculosis vaccine, which may enhance the BCG-induced immune response, is urgently needed. We assessed the safety of and characterized the T cell response induced by 3 doses of the candidate vaccine, MVA85A, in BCG-vaccinated infants from a setting where tuberculosis is endemic.
Infants aged 5-12 months were vaccinated intradermally with either 2.5 × 10(7), 5 × 10(7), or 10 × 10(7) plaque-forming units of MVA85A, or placebo. Adverse events were documented, and T-cell responses were assessed by interferon γ (IFN-γ) enzyme-linked immunospot assay and intracellular cytokine staining.
The 3 MVA85A doses were well tolerated, and no vaccine-related serious adverse events were recorded. MVA85A induced potent, durable T-cell responses, which exceeded prevaccination responses up to 168 d after vaccination. No dose-related differences in response magnitude were observed. Multiple CD4 T cell subsets were induced; polyfunctional CD4 T cells co-expressing T-helper cell 1 cytokines with or without granulocyte-macrophage colony-stimulating factor predominated. IFN-γ-expressing CD8 T cells, which peaked later than CD4 T cells, were also detectable.
MVA85A was safe and induced robust, polyfunctional, durable CD4 and CD8 T-cell responses in infants. These data support efficacy evaluation of MVA85A to prevent tuberculosis in infancy. Clinical Trials Registration. NCT00679159.
卡介苗（BCG）是唯一获得许可的结核病疫苗，对婴幼儿的肺部结核病提供的保护作用不佳。因此，急需一种新的结核病疫苗来增强卡介苗诱导的免疫应答。我们评估了候选疫苗 MVA85A 在结核病流行地区接种卡介苗的婴儿中的安全性，并对其诱导的 T 细胞应答进行了特征描述。
5-12 月龄婴儿皮内接种 2.5×10(7)、5×10(7)或 10×10(7)个空斑形成单位的 MVA85A 或安慰剂。记录不良反应，并通过干扰素 γ（IFN-γ）酶联免疫斑点测定法和细胞内细胞因子染色法评估 T 细胞应答。
3 种 MVA85A 剂量均具有良好的耐受性，且未记录到与疫苗相关的严重不良事件。MVA85A 诱导了强大、持久的 T 细胞应答，在接种后 168 d 内超过了接种前的应答。未观察到应答幅度与剂量相关的差异。诱导了多种 CD4 T 细胞亚群；表达辅助性 T 细胞 1 细胞因子的多功能 CD4 T 细胞与或不与粒细胞-巨噬细胞集落刺激因子共表达占优势。IFN-γ表达的 CD8 T 细胞在 CD4 T 细胞之后出现峰值，也可检测到。
MVA85A 是安全的，可在婴儿中诱导强大、多功能、持久的 CD4 和 CD8 T 细胞应答。这些数据支持对 MVA85A 进行预防婴儿结核病的疗效评估。临床试验注册。NCT00679159。
