Dendritic Cell-Targeted HIV Vaccine Product

树突状细胞靶向 HIV 疫苗产品

• 批准号: 8141876
• 负责人: Tibor Keler
• 金额: $ 29.76万
• 依托单位: CELLDEX THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8141876
• 关键词: AIDS/HIV problem; Address; Adjuvant; Agonist; Agreement; Antibodies; Antigens; Area; Attention; B-Lymphocytes; Binding; Biological Assay; Biotechnology; Cancer Patient; Cell Line; Cell physiology; Cellular Immunity; Cellular biology; Chimeric Proteins; Clinical; Clinical Trials; Collaborations; Country; Critical Pathways; Data; Dendritic Cells; Development; Development Plans; Economics; Employment; Engineering; Enhancers; Ensure; Evaluation; Gagging; Goals; Growth; HIV; HIV Antigens; HIV Envelope Protein gp120; HIV vaccine; High Pressure Liquid Chromatography; Human; Immune; Immune response; Immunity; Immunization; Immunoglobulin G; Immunology; Institution; Laboratories; Learning; Licensing; Lymphoid; Monkeys; Monoclonal Antibodies; Mus; Natural Immunity; Organ; Pattern recognition receptor; Phase; Poly ICLC; Process; Production; Proteins; Recombinant Antibody; Regimen; Relative (related person); Research; Research Activity; Secure; Seeds; Stimulus; Sum; T-Lymphocyte; Technology; Time; Transgenic Mice; Vaccines; arm; base; gag Gene Products; human monoclonal antibodies; immunogenicity; improved; innovation; manufacturing process; monomer; nonhuman primate; novel; pre-clinical; prevent; product development; prophylactic; receptor; recombinant viral vector; response; safety study; uptake

DESCRIPTION (provided by applicant): This proposal is a unique collaboration between a small, but full capability, Biotechnology Company and a premier academic institution and laboratory to develop a novel product for clinical trials in cancer patients. The project provides for additional employment and economic growth benefits through the development plan, and has the potential to have significant economic benefit if the treatment becomes successful. This proposal describes a vaccine product aimed to provide a feasible and nontoxic way to elicit strong immunity in humans to HIV proteins, and it will provide an added arm to vaccine strategies such as recombinant viral vectors. The technology behind this product is based on our most recent understanding of immunology and vaccines. First, the product ensures for the first time that HIV envelope and gag antigens are efficiently targeted to antigen presenting dendritic cells by using recombinant antibody technology. This vaccine product uses a human monoclonal antibody, generated by the PI's, that can seek out and bind to the subject's dendritic cells expressing the molecule DEC-205. In this way, a large number of dendritic cells in lymphoid organs can present antigens to rare antigen-specific T cells and efficiently initiate the immune attack against HIV proteins. Second, the product includes a stimulus or adjuvant that results in a strong innate response, which in turn is required for the optimum immune response. This product encompasses proprietary immune activators with clinical and pre-clinical track record. Importantly, these agents have been secured for use in these products through licensing partnerships and agreements. Finally, the product has carefully selected specific HIV envelope and gag antigens. These antigens individually have documented immunogenicity in mice and monkeys, when delivered to DEC-205, and now need to be combined into a vaccine product suitable for further development in phase II in mice and monkeys. PUBLIC HEALTH RELEVANCE: Dendritic cells are critical for the initiation of immunity. This proposal will harness the capacities of dendritic cells to initiate antibody and cell-mediated immunity against HIV. In the phase I portion, we will produce an antibody that efficiently delivers two HIV proteins to dendritic cells, and we will carry out proof of concept for improved immunity by giving vaccine together with safe adjuvants or immune enhancers to humanized mice. This proposal therefore describes an innovative product that addresses the need to be able to use proteins in an effective and nontoxic way to elicit and boost immunity against HIV, offering the potential of considerable impact in our country and worldwide.

描述（由申请人提供）：该提案是一家小但充分的能力，生物技术公司与主要学术机构和实验室之间的独特合作，以开发用于癌症患者临床试验的新产品。该项目通过制定计划提供了额外的就业和经济增长福利，并有可能获得巨大的经济利益。 该提案描述了一种旨在提供可行且无毒的方式来引起人类对HIV蛋白的强大免疫力的疫苗产品，它将为诸如重组病毒载体之类的疫苗策略提供额外的臂。该产品背后的技术基于我们对免疫学和疫苗的最新理解。 首先，该产品首次通过使用重组抗体技术将HIV包膜和插入抗原有效地针对抗原呈现树突状细胞的靶向。该疫苗产物使用由PI产生的人类单克隆抗体，该抗体可以寻找并结合给受试者表达分子DEC-205的树突状细胞。这样，淋巴器官中的大量树突状细胞可以向罕见的抗原特异性T细胞呈现抗原，并有效启动针对HIV蛋白的免疫攻击。 其次，该产品包括刺激或辅助物，从而产生强烈的先天反应，而最佳免疫反应又需要。该产品包含具有临床和临床前记录的专有免疫激活剂。重要的是，这些代理商已通过许可合作伙伴关系和协议确保用于这些产品。 最后，该产品仔细选择了特定的HIV包膜和堵嘴抗原。这些抗原分别记录了小鼠和猴子中的免疫原性，当时将其递送至Dec-205，现在需要将其合并为适合于小鼠和猴子中II期进一步开发的疫苗产品。 公共卫生相关性：树突细胞对于启动免疫力至关重要。该建议将利用树突状细胞的能力启动抗体和细胞介导的对HIV的免疫力。在第一阶段的部分中，我们将产生一种抗体，该抗体有效地将两种HIV蛋白提供给树突状细胞，我们将通过将疫苗与安全的辅助剂或免疫增强剂一起为人道化的小鼠提供概念证明，以提高免疫力。因此，该提案描述了一种创新的产品，该产品解决了能够以有效且无毒的方式使用蛋白质来激发和增强对艾滋病毒的免疫力的需求，从而在我国和全球范围内产生了相当大的影响。