Application of mycobacterial proteomics to vaccine design:: Improved protection by Mycobacterium bovis BCG prime-Rv3407 DNA boost vaccination against tuberculosis
Application of mycobacterial proteomics to vaccine design:: Improved protection by Mycobacterium bovis BCG prime-Rv3407 DNA boost vaccination against tuberculosis
复制标题
DOI：
10.1128/iai.72.11.6471-6479.2004
复制
发表时间：
2004-11-01
影响因子：
3.1
通讯作者：
Kaufmann, SHE
中科院分区：
文献类型：
--
作者：
Mollenkopf, HJ;Grode, L;Kaufmann, SHE
来自结核分枝杆菌和卡介苗(BCG)比较蛋白质组分析的信息主要用于预测潜在的候选疫苗。通过比较蛋白质组分析确定的36种候选结核分枝杆菌DNA疫苗在小鼠模型中进行了评估，以防止低剂量的结核分枝杆菌气雾剂感染。我们确定了候选DNA疫苗Rv3407为保护性抗原，并通过计算预测和伽马干扰素ELISPOT试验分析了推测的主要组织相容性复合体I类表位。重要的是，我们发现DNA疫苗Rv3407在异种Prime-Boost疫苗接种方案中提高了卡介苗的效力。我们的数据证明了蛋白质组学、表位预测和广泛筛选假定抗原的组合用于鉴定新的DNA疫苗候选的基本原理。此外，我们的实验表明，与单独接种卡介苗相比，在卡介苗引爆剂的“顶端”接种异种优质加强疫苗可提供更好的预防结核病的效果。
Information from comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guerin (BCG) principally allows prediction of potential vaccine candidates. Thirty-six M. tuberculosis DNA vaccine candidates identified by comparative proteome analysis were evaluated in the mouse model for protection against low-dose aerosol M. tuberculosis infection. We identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed putative major histocompatibility complex class I epitopes by computational predictions and gamma interferon Elispot assays. Importantly, we discovered that the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous prime-boost vaccination protocol. Our data demonstrate the rationale of a combination of proteomics, epitope prediction, and broad screening of putative antigens for identification of novel DNA vaccine candidates. Furthermore, our experiments show that heterologous prime-boost vaccination with a defined antigen boost "on top" of a BCG primer provides superior protection against tuberculosis over vaccination with BCG alone.