Enhancing B cell immunity against HIV-1 using novel vaccine delivery platforms

使用新型疫苗递送平台增强 B 细胞针对 HIV-1 的免疫力

• 批准号: 8117745
• 负责人: Michael W Cho
• 金额: $ 124.63万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8117745
• 关键词: Enhancing; cell; immunity; against; HIV

DESCRIPTION (provided by applicant): There is a global urgency to develop a protective AIDS vaccine. Neutralizing antibodies (Nabs) can provide effective prophylaxis against HIV-1 infections. Although eliciting Nabs that are broadly cross-reactive has long been a major scientific challenge, we have recently generated a mini-protein containing the membrane-proximal external region (MPER) of gp41 that can elicit Nabs with significant breadth. The primary objective of this proposal is to develop novel vaccine delivery platforms that can enhance B cell immune responses. The underlying hypothesis behind this proposal is that a polymeric antigen containing many copies of the same target epitope in a repetitive, well-defined lattice (multivalent) can elicit a superior B cell immune response than a monomeric antigen (monovalent) because of its potential to (1) induce both T cell-independent (Tl) and -dependent (TD) B cell immunity; (2) enhance B cell activation and maturation; and (3) activate a greater diversity of B cell subsets. To test this hypothesis, we will develop novel vaccine delivery platforms based on nanostructures designed to present multivalent forms of immunogens and costimulatory molecules to B cells and to facilitate targeted delivery of antigens to dendritic cells and macrophages. Successful completion of the proposed studies would represent a major advancement towards developing a protective AIDS vaccine. The proposed research Program consists of two Projects and two Cores: The role of Project 1 is to develop vaccine delivery platforms. The role of Project 2 is to evaluate B cell immune responses against gp41- MPER in great detail. The Administrative Core is responsible for providing the organizational management and maintaining infrastructure to support the fiscal monitoring. The Protein Production Core is responsible for producing and providing high quality antigens and costimulatory molecules to Projects 1 and 2. This is a highly collaborative program project of seven key investigators from five institutions.

描述（由申请人提供）：有一个全球迫切的迫切性来开发一种保护性艾滋病疫苗。中和抗体（NABS）可以为HIV-1感染提供有效的预防。尽管引起广泛交叉反应的NAB长期以来一直是一个重大的科学挑战，但我们最近产生了一种含有GP41的膜外部区域（MPER）的迷你蛋白质，该蛋白质可以引起具有显着宽度的NAB。该提案的主要目的是开发新型的疫苗输送平台，以增强B细胞免疫反应。 该提案背后的基本假设是，在重复的，定义明确的晶格中包含许多相同靶位副本的聚合物抗原可以引起比单元抗原（单元）的优质B细胞免疫反应，因为它的潜力是（1）对（1）诱导T细胞依赖性（1）依赖性（tl）和 - 依赖性（tl）和 - deptent（tdeptent）; （2）增强B细胞的激活和成熟； （3）激活B细胞子集的多样性。为了检验这一假设，我们将基于纳米结构开发新型的疫苗输送平台，该纳米结构旨在呈现多用形式的免疫原子和加时刺激分子向B细胞呈现，并促进靶向抗原向树突状细胞和巨噬细胞的靶向递送。成功完成拟议的研究将代表开发保护性艾滋病疫苗的重大进步。 拟议的研究计划由两个项目和两个核心组成：项目1的作用是开发疫苗输送平台。项目2的作用是评估B细胞免疫反应针对GP41- MPer的详细措施。行政核心负责提供组织管理和维护基础架构以支持财政监控。蛋白质生产核心负责为项目1和2提供高质量的抗原和共刺激分子。这是来自五个机构的七位主要调查员的高度协作计划项目。