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（由申请人提供）： 自身免疫性糖尿病（1型糖尿病; T1 D）是一种免疫调节失败的疾病。T1 D疫苗旨在使用抗原物质刺激调节性免疫应答并恢复免疫稳态。成功实施的挑战包括找到最佳的接种方式和疫苗有效的最佳佐剂。我们组建了一个生物材料和T1 D专家团队来应对这些挑战。这项工作的目标是研究纳入T1 D疫苗的控释生物材料递送系统的相关疫苗组分的递送。以受控方式靶向和递送免疫调节因子至关键免疫缺陷的能力 免疫细胞类型是关键我们的策略包括注射因子（例如，抗原和佐剂）配制在与佐剂和包封胰岛素抗原的可生物降解微粒共混合的可注射的原位形成的水凝胶中。此处采用的佐剂策略是沿着最近的T1 D临床试验的路线（显示安全性但不有效），施用促炎佐剂加抗原，期望炎症可以通过随后对胰腺抗原的耐受性而消退。这种生物材料输送系统作为一个临时的微环境来吸引和培养免疫细胞。我们假设这种基于生物材料的疫苗系统将招募和教育免疫细胞对胰岛素产生耐受性，从而改善T1 D。拟议的研究是创新的，代表了疫苗成分的靶向、受控递送，旨在恢复对T1 D自身抗原的耐受性。我们的体内初步数据表明，我们的方法是有希望的改善T1 D。