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；T1D）是一种免疫调节失败的疾病。T1D疫苗旨在使用抗原物质刺激调节免疫反应并恢复免疫稳态。成功实施的挑战包括找到最佳的递送方式和疫苗有效的最佳佐剂。我们已经组建了一个生物材料和T1D领域的专家团队来应对这些挑战。这项工作的目的是研究将相关疫苗成分纳入T1D疫苗控释生物材料递送系统的递送。以可控的方式靶向和递送免疫调节因子的能力至关重要