Evaluation of the immunogenicity of pBudCE4.1 plasmids encoding mycolyl-transferase Ag85A and phosphate transport receptor PstS-3 from Mycobacterium tuberculosis

Evaluation of the immunogenicity of pBudCE4.1 plasmids encoding mycolyl-transferase Ag85A and phosphate transport receptor PstS-3 from Mycobacterium tuberculosis
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DOI:
10.1016/j.vaccine.2005.08.035
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发表时间:
2006-05-22
期刊:
影响因子:
5.5
通讯作者:
Huygen, Kris
Huygen, Kris
中科院分区:
医学3区
文献类型:
--
作者:
Romano, Marta;Roupie, Virginie;Huygen, Kris

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由结核分枝杆菌 (Mtb) 引起的结核病 (TB) 仍然是一个主要的健康问题。目前唯一可用的疫苗卡介苗只能提供可变的保护,因此迫切需要改进的疫苗。给予编码分泌型菌基转移酶 Ag85A 和表面暴露的磷酸盐转运受体 PstS-3 的 DNA 疫苗可引发能够保护受 Mtb 攻击的小鼠的免疫反应。为了结合这两种DNA疫苗诱导的针对Mtb感染的保护作用,我们将Ag85A和PstS-3克隆到pBudCE4.1载体中,其中抗原表达由两个独立的启动子控制。 (BALB/cxC57BL/6)F1 小鼠接种了该组合疫苗,并将免疫反应与接种编码 pBudCE4.1 或 pV1J.ns-tPA 主链上单一抗原的质粒所诱导的免疫反应进行了比较。针对 Ag85A 的抗体和 Th1 型细胞因子反应相当,而在用组合质粒疫苗接种的小鼠中,针对 PstS-3 的反应明显较低,这表明与作为主要抗原的霉菌基转移酶的抗原竞争。 (c) 2005 Elsevier Ltd. 保留所有权利。
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), remains a major health problem. The only currently available vaccine, BCG, confers only variable protection and an improved vaccine is urgently needed. Administration of DNA vaccines encoding the secreted mycolyl-transferase Ag85A and the surface-exposed phosphate transport receptor PstS-3 elicit an immune response capable of protecting mice challenged with Mtb. In order to combine the protection against Mtb infection induced by these two DNA vaccines, we have cloned Ag85A and PstS-3 in pBudCE4.1 vector, in which antigenic expression is controlled by two independent promoters. (BALB/cxC57BL/6)F1 mice were vaccinated with this combination vaccine and immune responses were compared to those induced by vaccination with plasmids encoding the single antigens on pBudCE4.1 or pV1J.ns-tPA backbone. Antibody and Th1 type cytokine responses against Ag85A were comparable, whereas responses against PstS-3 were clearly lower in mice vaccinated with the combination plasmid, suggesting antigenic competition with the mycolyl-transferase being the dominant antigen. (c) 2005 Elsevier Ltd. All rights reserved.