Fralish Bolyn H, Tarleton Rick L
Department of Cellular Biology, Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA.
Vaccine. 2003 Jun 20;21(21-22):3070-80. doi: 10.1016/s0264-410x(03)00121-x.
Genetic immunization with a limited set of genes has been demonstrated to be an effective means of protecting mice from a normally lethal challenge of Trypanosoma cruzi. The goal of this study was to expand the diversity of genes assessed as genetic vaccine candidates. Screening a T. cruzi amastigote cDNA expression library with anti-amastigote monoclonal antibodies resulted in the identification of two genes, the previously identified flagellar Ca(2+) binding protein, FCaBP, and a novel homologue of the adaptin AP-3 complex beta3 subunit, Tcbeta3. A third gene, LYT1, recently identified as a secreted T. cruzi protein involved in cell lysis and infectivity, and was selected. Although peptides from all three genes were found to be targets of cytotoxic T cell responses in chronically infected mice, only immunization with LYT1 protected mice from a normally lethal challenge of T. cruzi. As an alternative to testing individual T. cruzi genes as vaccines, pools of genes from the trans-sialidase (TS) and mucin families were assessed in vaccination studies. Immunization with pools of TS but not mucin genes provided protection against a normally lethal challenge of T. cruzi. This study demonstrates that the ability of T. cruzi proteins to elicit immune responses in infected hosts does not necessarily associate with the ability to induce protection and that both the products of single genes and multi-gene families may serve as effective vaccines.
已证明用一组有限的基因进行基因免疫是保护小鼠免受克氏锥虫正常致死性攻击的有效方法。本研究的目的是扩大作为基因疫苗候选物评估的基因的多样性。用抗无鞭毛体单克隆抗体筛选克氏锥虫无鞭毛体cDNA表达文库，鉴定出两个基因，即先前鉴定的鞭毛钙结合蛋白FCaBP和衔接蛋白AP-3复合物β3亚基的新同源物Tcbeta3。第三个基因LYT1，最近被鉴定为参与细胞裂解和感染性的克氏锥虫分泌蛋白，并被选中。尽管在慢性感染小鼠中发现来自所有三个基因的肽都是细胞毒性T细胞反应的靶标，但只有用LYT1免疫才能保护小鼠免受克氏锥虫正常致死性攻击。作为测试单个克氏锥虫基因作为疫苗替代品的方法，在疫苗接种研究中评估了转唾液酸酶（TS）和粘蛋白家族的基因库。用TS基因库而非粘蛋白基因库免疫可提供针对克氏锥虫正常致死性攻击的保护。这项研究表明，克氏锥虫蛋白在感染宿主中引发免疫反应的能力不一定与诱导保护的能力相关，单个基因和多基因家族的产物都可作为有效的疫苗。
