B lymphocytes as antigen-presenting cell-based genetic vaccines.
B lymphocytes as antigen-presenting cell-based genetic vaccines.
复制标题
B 淋巴细胞作为基于抗原呈递细胞的基因疫苗。
DOI：
10.1111/j.0105-2896.2004.00152.x
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发表时间：
2004
影响因子：
8.7
通讯作者：
Gerloni,Mara
中科院分区：
文献类型：
--
作者：
Zanetti,Maurizio;Castiglioni,Paola;Rizzi,Marta;Wheeler,Matthew;Gerloni,Mara
质粒DNA接种是一种简单的免疫方法，但其免疫原性较低，阻碍了有效的人用DNA疫苗的开发。在这里，我们讨论了如何解决免疫原性差的问题，并提出了我们的建议：基因编程B淋巴细胞作为抗原呈递细胞（APC）疫苗。首先，我们证明成熟的B淋巴细胞自发地吸收质粒DNA，即在没有任何促进分子或事件的情况下，自发的淋巴细胞转基因。其次，我们证明了转基因B淋巴细胞很容易和可复制地转化为功能性apc，具有双重特征：共刺激分子上调和内源性抗原合成。在小鼠体内作为免疫原，转基因B淋巴细胞在单次静脉注射后诱导强大且持久的T细胞免疫。令人惊讶的是，单次静脉注射3 × 102转基因淋巴细胞可获得免疫和对致命病毒攻击的保护。讨论了这种新方法的优势，即利用基因程序化的B淋巴细胞靶向二级淋巴器官的优势，以及低抗原剂量的优势。我们认为这些特性反映在简单的特征上，如时间同步性和初始定位于次要淋巴器官的APCs，赋予了长期的合成和抗原向T细胞的递呈。
Inoculation of plasmid DNA is a simple way to immunize, but it is characterized by low immunogenicity, which has hampered the development of effective DNA vaccines for human use. Here, we discuss how poor immunogenicity can be solved and present our proposal: genetically programmed B lymphocytes as antigen‐presenting cell (APC) vaccines. First, we demonstrate that mature B lymphocytes take up plasmid DNA spontaneously, i.e., in the absence of any facilitating molecule or event, spontaneous lymphocyte transgenesis. Second, we demonstrate that transgenic B lymphocytes are easily and reproducibly turned into functional APCs with dual characteristics: upregulation of costimulatory molecules and endogenous synthesis of antigen. Used as immunogens in mice, transgenic B lymphocytes induce robust and long‐lasting T‐cell immunity after single intravenous injection. Surprisingly, immunity and protection against lethal virus challenge can be obtained with a single intravenous injection of 3 × 102transgenic lymphocytes. The new approach is discussed relative to the advantage of targeting secondary lymphoid organs with genetically programmed B lymphocytes and the advantage offered with respect to low antigen dose. We suggest that these properties reflect on simple characteristics, such as time synchronization and initial localization to secondary lymphoid organs of APCs endowed with protracted synthesis and presentation of antigen to T cells.