Biomaterial Delivery System for Type 1 Diabetes Vaccine

1 型糖尿病疫苗的生物材料输送系统

• 批准号: 8761784
• 负责人: Benjamin George Keselowsky
• 金额: $ 37.42万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8761784
• 关键词: Address; Adjuvant; Antigen Presentation Pathway; Antigens; Autoantigens; Autoimmune Diabetes; Autoimmune Diseases; Autoimmune Responses; B-insulin; Biocompatible Materials; Cells; Clinical Trials; Data; Diabetes Mellitus; Disease; Encapsulated; Engineering; Gel; Glycolic-Lactic Acid Polyester; Goals; Homeostasis; Hydrogels; Immune; Immune response; Immune system; Immunosuppressive Agents; In Situ; Inbred NOD Mice; Inflammation; Inflammatory; Injectable; Injection of therapeutic agent; Insulin; Insulin-Dependent Diabetes Mellitus; Life; Pancreas; Pathway interactions; Peptides; Phagocytes; Prevention; Property; Recruitment Activity; Regulation; Research; Safety; System; T-Lymphocyte; Therapeutic; Vaccination; Vaccine Adjuvant; Vaccines; Work; base; cell type; clinically relevant; controlled release; economic impact; expectation; in vivo; innovation; insulin tolerance; particle; public health relevance; scaffold; subcutaneous; vaccine delivery

DESCRIPTION (provided by applicant): Autoimmune diabetes (type 1 diabetes; T1D) is a disease of failed immune regulation. A vaccine for T1D aims to use antigenic material to stimulate regulatory immune responses and restore immune homeostasis. Challenges for successful implementation include finding the best mode of delivery and the best adjuvant for the vaccine to be effective. We have assembled a team of experts in biomaterials and T1D to address these challenges. The goal of this work is to investigate the delivery of relevant vaccine components incorporated into a controlled release biomaterial delivery system for a T1D vaccine. The ability to target and deliver immunomodulating factors in a controlled way to critical immune cell types is key. Our strategy involves the injectable administration of factors (e.g., antigen and adjuvant) formulated in an injectable, in-situ forming hydrogel co-mixed with adjuvant and biodegradable microparticles encapsulating insulin antigen. The adjuvant strategy taken here is along the lines of recent clinical trials for T1D (showing safety but not efficacy), administering pro-inflammatory adjuvants plus antigen with the expectation that inflammation can be resolved with subsequent tolerance to pancreatic antigen. This biomaterial delivery system serves as a temporary microenvironment to attract and educate immune cells. We hypothesize this biomaterial-based vaccine system will recruit and educate immune cells to become tolerant of insulin, ameliorating T1D. The proposed research is innovative, representing targeted, controlled delivery of vaccine components aiming to restore tolerance to T1D self-antigens. Our in vivo preliminary data demonstrate that our approach is promising for the amelioration of T1D.

描述(申请人提供)：自身免疫性糖尿病(1型糖尿病；T1D)是一种免疫调节失败的疾病。一种针对T1D的疫苗旨在使用抗原性材料刺激调节性免疫反应，恢复免疫动态平衡。成功实施的挑战包括找到疫苗有效的最佳投放方式和最佳佐剂。我们已经组建了一支由生物材料和T1D领域的专家组成的团队来应对这些挑战。这项工作的目标是研究被纳入T1D疫苗的控释生物材料递送系统的相关疫苗组件的递送。靶向免疫调节因子并以受控方式将其传递给危重患者的能力 免疫细胞类型是关键。我们的策略包括注射注射因子(如抗原和佐剂)，形成一种可注射的原位形成的水凝胶，与包裹胰岛素抗原的佐剂和可生物降解的微粒共同混合。这里采用的佐剂策略与最近的T1D临床试验(显示安全但不有效)相同，使用促炎佐剂和抗原，期望炎症可以在随后对胰腺抗原耐受的情况下得到缓解。这种生物材料输送系统作为一个临时的微环境来吸引和教育免疫细胞。我们假设这种基于生物材料的疫苗系统将招募和培养免疫细胞，使其对胰岛素耐受，从而改善T1D。这项拟议的研究是创新的，代表了有针对性的、受控的疫苗成分输送，旨在恢复对T1D自身抗原的耐受性。我们在体内的初步数据表明，我们的方法对于改善T1D是有希望的。