Biomaterial Delivery System for Type 1 Diabetes Vaccine

1 型糖尿病疫苗的生物材料输送系统

基本信息

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
项目类别：
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

项目摘要

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。 T1D 疫苗旨在利用抗原物质刺激调节性免疫反应并恢复免疫稳态。成功实施的挑战包括寻找最佳的给药方式和使疫苗有效的最佳佐剂。我们组建了一支生物材料和 T1D 专家团队来应对这些挑战。这项工作的目标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中的递送。以受控方式靶向和递送免疫调节因子至关键部位的能力免疫细胞类型是关键。我们的策略涉及注射给药因子（例如抗原和佐剂），其配制在可注射的原位形成水凝胶中，与佐剂和封装胰岛素抗原的可生物降解微粒混合。这里采取的佐剂策略与最近 T1D 临床试验的思路一致（显示安全性但不功效），施用促炎佐剂加抗原，期望炎症能够得到解决，随后对胰腺抗原产生耐受。这种生物材料输送系统充当临时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教育免疫细胞对胰岛素产生耐受性，从而改善 1 型糖尿病。拟议的研究具有创新性，代表了疫苗成分的定向、受控递送，旨在恢复对 T1D 自身抗原的耐受性。我们的体内初步数据表明，我们的方法有望改善 T1D。