B Cell Related Prophylaxis and Therapeutics

针对生物武器和生物恐怖制剂的特异性抗体可以发展成为一种强大的 我们的防御武器。RCE申请的这一部分建议开发新的 利用体液和细胞介导的免疫力对抗选择的生物制剂的潜力的策略 战本节包括基于被动和主动免疫的方法， 补充解决动员免疫反应的问题。被动免疫是 目前，提供立即免疫以保护处于风险中的易感个体的唯一手段是 生物战然而，尽管经过了世纪的研究，我们仍然无法预测 抗体结构、特异性、亲和力和功效。被动免疫部分的重点是 三种选择剂，炭疽杆菌，金黄色葡萄球菌肠毒素和西尼罗河病毒， 3个目的：1）制备抗炭疽毒素蛋白的中和性单克隆抗体（鼠和人） components，S.金黄色葡萄球菌肠毒素和西尼罗病毒包膜; 2）鉴定抗体属性 3）为了产生非常高亲和力的中和活性， 活化诱导脱氨酶（AID）。主动免疫能使宿主产生免疫力， 它的优点是提供持久的保护。主动免疫部分侧重于两个方面 选择剂：鼠疫耶尔森氏菌和炭疽杆菌，并有三个具体目标：1）开发有效的 通过鉴定树突状细胞（DC）受体，刺激T细胞和B细胞的功能， 疫苗抗原在体内的有效摄取和呈递，以及成熟DC的佐剂，包括 DC亚群; 2）为了操纵边缘区巨噬细胞，其含有DC亚群的专门亚群。 巨噬细胞和DC以引发T细胞非依赖性抗体应答; 3）鉴定新的化学物质 刺激由B选择性表达的不同的Toll样受体RP-105的化合物。细胞我们 预计拟议的研究将导致用于治疗用途的抗体，更好地了解 抗体结构和功能的关系，以及利用最近的 我们对树突状细胞、巨噬细胞和B细胞生物学的理解取得了进展。

Specific antibody to biological weapons and agents of bioterrorism can be developed into a powerful component of our defensive arsenal. This section of the RCE application proposes to develop novel strategies to harness the potential of humoral and cell-mediated immunity against select agents of biological warfare. The section includes passive and active immunization-based approaches, which are complementary solutions to the problem of mobilizing the immune response. Passive immunization is currently the only means of providing immediate immunity to protect susceptible individuals at risk for biological warfare. However, despite over a century of study we still cannot predict the relationship between antibody structure, specificity, affinity and efficacy. The passive immunization component is focused on three select agents, Bacillus anthracis, Staphylococcal aureus enterotoxin, and West Nile virus and has three aims: 1) To produce neutralizing (murine and human) monoclonal antibodies to anthrax toxin protein components, S. aureus enterotoxin, and West Nile virus envelope; 2) To identify the antibody attributes necessary for optimal toxin and viral neutralizing activity; 3) To generate very high affinity neutralizing of activation induced deaminase (AID). Active immunization can make the host immune and has the advantage that it provides long lasting protection. The active immunization component is focused on two select agents: Yersinia pestis and Bacillus anthracis and has three specific aims: 1) To develop potent stimulatory function for T cells and B cells by identifying dendritic cell (DC) receptors that lead to more efficient uptake and presentation of vaccine antigens in vivo, as well as adjuvants that mature DCs including DC subsets; 2) To manipulate the marginal zone macrophages which contains specialized subsets of macrophages and DCs to elicit T cell independent antibody responses; 3) To identify new chemical compounds that stimulate a distinct toll-like receptor, RP-105, selectively expressed by B. cells. We anticipate that the proposed studies will lead to antibodies for therapeutic use, a better understanding of the relationship of antibody structure and function, and novel approaches to vaccination that exploit recent advances in our understanding of dendritic cell, macrophage and B cell biology.