Identification of Mycobacterium tuberculosis vaccine candidates using human CD4+ T-cells expression cloning
Identification of Mycobacterium tuberculosis vaccine candidates using human CD4+ T-cells expression cloning
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DOI：
10.1016/j.vaccine.2008.10.056
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发表时间：
2009-01-07
期刊：
影响因子：
5.5
通讯作者：
Alderson, Mark R.
中科院分区：
文献类型：
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作者：
Coler, Rhea N.;Dillon, Davin C.;Alderson, Mark R.
为了鉴定结核分枝杆菌（Mtb）抗原作为抗结核（TB）亚单位疫苗的候选抗原，我们采用了CD 4（+）T细胞表达筛选方法。用不同的抗原底物刺激来自9名健康PPD阳性供体的Mtb特异性CD 4（+）T细胞系，包括用Mtb感染的自体树突状细胞（DC），或用培养滤液蛋白（CFP）、抗Mtb纯化蛋白衍生物（PPD）培养。这些细胞系用于筛选在大肠杆菌中表达并由自体DC加工和呈递的基因组Mtb文库。这种筛选导致回收了许多T细胞抗原，包括新的和先前描述的抗原。这些新的抗原之一，称为Mtb9.8（Rv 0287），被多种T细胞系识别，用Mtb感染的DC或CFP刺激。使用TB的小鼠和豚鼠模型，产生了高水平的IFN-γ，并且在用在AS 02 A或AS 01 B佐剂系统中配制的Mtb9.8免疫后观察到针对Mtb攻击的固体保护。这些结果表明，Mtb基因组的T细胞筛选可用于鉴定作为疫苗开发候选物的CD 4（+）T细胞抗原。(C)2008爱思唯尔有限公司保留所有权利。
To identify Mycobacterium tuberculosis (Mtb) antigens as candidates for a subunit vaccine against tuberculosis (TB), we have employed a CD4(+) T-cell expression screening method. Mtb-specific CD4(+) T-cell lines from nine healthy PPD positive donors were stimulated with different antigenic substrates including autologous dendritic cells (DC) infected with Mtb, or cultured with culture filtrate proteins (CFP), anti purified protein derivative of Mtb (PPD). These lines were used to screen a genomic Mtb library expressed in Escherichia coli and processed and presented by autologous DC. This screening led to the recovery of numerous T-cell antigens, including both novel and previously described antigens. One of these novel antigens, referred to as Mtb9.8 (Rv0287), was recognized by multiple T-cell lines, stimulated with either Mtb-infected DC or CFP. Using the mouse and guinea pig models of TB, high levels of IFN-gamma were produced, and solid protection from Mtb challenge was observed following immunization with Mtb9.8 formulated in either AS02A or AS01B Adjuvant Systems. These results demonstrate that T-cell screening of the Mtb genome can be used to identify CD4(+) T-cell antigens that are candidates for vaccine development. (C) 2008 Elsevier Ltd. All rights reserved.