Transgenic B-Cell Immunogenes

描述：(改编自申请者摘要)：在本创新补助金中 我们提出了一种新的疫苗途径来诱导抗病毒CTL。新的方法是 基于一种新的概念，使用转基因淋巴细胞来编程免疫 作为内源性合成抗原和抗原的底物的反应 展示功能完美地结合在一起。在试点实验中，我们已经获得了 初步证据表明，转基因淋巴细胞免疫有助于 仅一次注射103个细胞即可产生强大的CTL反应。此应用程序 打算对这一令人兴奋的观察结果进行扩展。我们的目标是确定B 淋巴细胞是推动免疫的枢纽，并了解 与体内保护有关的系统。我们将考虑以下参数 当Extent 01在体外用肽培养前后裂解时， 四聚体染色计数效应器CTL及其亲和力 抗原/MHC复合体的受体。这些参数将在 用病毒进行体内激发和激发。最后，CTL响应将是 在Th细胞帮助下和不在Th细胞帮助下诱导。我们研究的中心将是一个 我们的新方法与目前使用的一些方法的比较 诱导CTL，特别是多肽冲击的树突状细胞疫苗。一次证明 结果表明，转基因淋巴细胞 免疫是诱导保护性抗病毒CTL的有效方法 回应，成本效益考虑将使转基因淋巴细胞 免疫接种--一种非常可取的艾滋病毒疫苗接种新方法 感染。

DESCRIPTION: (Adapted from the Applicant's Abstract): In this Innovation Grant we propose a new vaccine approach to induce anti-virus CTL. The new approach is based on a new concept, the use of transgenic lymphocytes to program the immune response as the substrate in which endogenous synthesis of antigen and antigen presenting function are ideally combined. In pilot experiments we have obtained initial evidence that transgenic lymphocyte immunization lends itself to a robust CTL response with a single injection of just 103 cells. This application intends to expand on this exciting observation. Our goal is to determine that B lymphocytes are the pivot driving immunization, and understand the biology of the system in relation to protection in vivo. We will consider parameters such as the extent 01 lyses prior and after in vitro culture with peptide, the enumeration of effector CTL by tetramer staining, and the affinity of their receptor for the antigen/MHC complex. These parameters will be assessed during priming and after in vivo challenge with virus. Finally, CTL responses will be induced with and without Th cell help. Central to our studies will be a comparison between our new approach with some of the approaches currently used to induce CTL, in particular peptide-pulsed dendritic cell vaccines. Once proof of principle is obtained and results will show that transgenic lymphocyte immunization is an effective method to induce protective anti-viral CTL responses, cost effectiveness considerations will make transgenic lymphocyte immunization a very desirable new approach for vaccination against HIV infection.