Dose-Finding Study of the Novel Tuberculosis Vaccine, MVA85A, in Healthy BCG-Vaccinated Infants
Dose-Finding Study of the Novel Tuberculosis Vaccine, MVA85A, in Healthy BCG-Vaccinated Infants
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DOI：
10.1093/infdis/jir195
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发表时间：
2011-06-15
影响因子：
6.4
通讯作者：
McShane, Helen
中科院分区：
文献类型：
--
作者：
Scriba, Thomas J.;Tameris, Michele;McShane, Helen
背景卡介苗是唯一获得许可的结核病疫苗，对婴儿和儿童的肺结核保护作用很差。迫切需要一种新的结核病疫苗，它可以增强卡介苗诱导的免疫反应。我们评估了3剂候选疫苗MVA 85 A在结核病流行的BCG接种婴儿中诱导的T细胞应答的安全性和特征。5-12个月大的婴儿皮内接种2.5 × 10（7）、5 × 10（7）或10 × 10（7）噬斑形成单位的MVA 85 A或安慰剂。记录不良事件，并通过干扰素-γ（IFN-γ）酶联免疫斑点试验和细胞内细胞因子染色评估T细胞应答。3种MVA 85 A剂量耐受性良好，未记录到疫苗相关的严重不良事件。MVA 85 A诱导有效的，持久的T细胞反应，超过接种后168天接种前的反应。未观察到反应幅度的剂量相关差异。诱导多种CD 4 T细胞亚群;多功能CD 4 T细胞共表达辅助性T细胞1细胞因子，有或没有粒细胞-巨噬细胞集落刺激因子占主导地位。IFN-γ表达的CD 8 T细胞，其峰值晚于CD 4 T细胞，也是可检测的。MVA 85 A是安全的，并在婴儿中诱导稳健的、多功能的、持久的CD 4和CD 8 T细胞应答。这些数据支持MVA 85 A预防婴儿结核病的有效性评价。NCT 00679159。
Background. 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.Methods. Infants aged 5-12 months were vaccinated intradermally with either 2.5 x 10(7), 5 x 10(7), or 10 x 10(7) plaque-forming units of MVA85A, or placebo. Adverse events were documented, and T-cell responses were assessed by interferon gamma (IFN-gamma) enzyme-linked immunospot assay and intracellular cytokine staining.Results. 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-gamma-expressing CD8 T cells, which peaked later than CD4 T cells, were also detectable.Conclusions. 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.