Human Monoclonal Antibodies

直接从免疫供体分离抗体提供了充分利用抗体强度的优势。 人类抗体对疫苗接种或感染的反应。通过跟踪抗原特异性的 通过分析B细胞群的抗体，我们可以直接调查B细胞群， 功能在我们的人单克隆抗体技术开发项目（TOP）的竞争性更新中， 抗体我们联合收割机结合了两种独特的强大的新技术， 允许对人B细胞特异性进行质量上的有效分析。一种由Dr. Lanzavecchia等人通过有效生产单克隆抗体，提供了对B细胞特异性的整个历史的分析 从长期记忆B细胞室中分离出来。威尔逊和艾哈迈德的第二项技术 实验室仔细检查当前正在进行的浆母细胞特异性，并产生大量的抗原特异性 在短时间内产生主要对抗原特异的抗体。我们将使用这些工具， 解决有关人类B细胞对黄热病病毒（YFV）和登革热的反应的基本问题 病毒通过结合这些强大的产生人单克隆抗体（浆母细胞和记忆B细胞）的平台， 我们应该能够全面分析人类B细胞对这些病毒的反应，并探测 记忆B细胞和抗体分泌浆细胞之间的关系。 因为产生的抗体是完全人类的，所以它们可以产生有价值的诊断，并允许更安全的 药物比嵌合或人源化抗体。因此，除了解决这些基本问题外， 问题，我们提出的研究也应该导致一个大的面板的人类单克隆抗体的发展 针对YFV和登革热-两种黄病毒是重要的公共卫生问题，是高度优先考虑的 生物防御病原体提出了三个具体目标：1）表征原代人B细胞 对YFV-17 D的应答导致ASC和长期记忆B细胞的产生; 2）分析 动力学，可变基因库，和特异性的ASC和记忆细胞诱导加强 接种YFV-17 D。3)表征人B细胞对急性登革病毒感染的应答， 孩子

The isolation of antibodies directly from immune donors offers the advantage of fully exploiting the strength of the human antibody response to vaccination or infection. By following the developmental fate of antigenspecific B cell populations through analysis of their antibodies we can generate a direct survey of B cell function. In this competitive renewal of our Technology Development Project (TOP) on Human Monoclonal Antibodies we combine two uniquely powerful new technologies recently developed that for the first time allow the efficient analysis of human B cell specificity en mass. One approach pioneered by Dr. Lanzavecchia, provides an analysis of the entire history of B cell specificities by efficiently producing mAbs from the long-term memory B cell compartment. The second technology from the Wilson and Ahmed laboratories scrutinizes current, ongoing plasmablast specificities and generates large numbers of antigenspecific antibodies in a short time that are predominantly specific to the antigens. We will use these tools to address fundamental questions about the human B cell response to yellow fever virus (YFV) and dengue virus. By combining these powerful platforms of generating human mAbs (plasmablasts and memory B cells) we should be able to comprehensively analyze the human B cell response to these viruses and to probe the relationship between memory B cells and antibody secreting plasma cells. Because the antibodies produced are fully human they can yield valuable diagnostics and allow for safer Pharmaceuticals than chimeric or humanized antibodies. Thus, in addition to addressing these fundamental questions, our proposed studies should also result in the development of a large panel of human mAbs against YFV and dengue - two flaviviruses that are of important public health concern and are high priority biodefense pathogens. Three specific aims are proposed: 1) Characterize the primary human B cell response to YFV-17D leading to the generation of ASCs and long-term memory B cells; 2) Analyze the dynamics, variable gene repertoire, and the specificity of ASC and memory cells induced by booster vaccination with YFV-17D. 3) Characterize the human B cell response to acute dengue virus infection of Children.