A polymeric biomaterial-based vaccine utilizing immunomodulatory agents and antigen for the amelioration of type 1 diabetes.

免疫介导的疾病，如1型糖尿病（T1 D）、多发性硬化症、类风湿性关节炎和 系统性红斑狼疮在美国已达到流行病的程度。T1 D影响估计1.25 每年有超过30，000名新患者被诊断出来，估计造成15，000美元的收入。 到2024年，美国的医疗保健成本将达到10亿美元。T1 D是一种自身免疫性疾病，其特征在于效应T细胞 介导的胰岛素产生β细胞的破坏，使患者无法产生胰岛素， 迫使患者不断地监测他们的葡萄糖水平 他们的生活。最终，葡萄糖代谢中断，导致危及生命的发展 心脏病和肾衰竭等并发症。显然，与治疗和护理相关的费用 在美国，T1 D对社会和个人都很重要，迫切需要一种新的治疗方法， 阻止这种异常的自身免疫活动。这是OneVax致力于满足的需求。 生物医学研究界一直在寻找更好的方法来诱导特异性免疫耐受， 将近50年了使用免疫调节剂的临床干预试验（例如，抗CD 3）未能 满足临床终点，尽管I/II期试验结果积极。此外，传统的疫苗策略 单独提供自身抗原或肽不能充分阻断进行中的β细胞免疫。因此，新的 需要一种既有效又持久的治疗策略来有效地阻止T1 D的持续发作。 利用树突状细胞（DC）的T1 D治疗性疫苗接种方法有望纠正抗原- 特异性自身免疫应答，但目前涉及DC的外源性操作的策略是不稳定的， 效率低且昂贵。OneVax已经开发了一种新型的体内致耐受性疫苗， 将免疫调节因子施用至吞噬DC的组分（指定为OV-01）， 有效的抗原呈递细胞类型的身体和免疫系统的关键调节器。OV-01最低限度 侵入性，不需要昂贵的细胞分离和储存，并且由于其稳定的组成，具有延长的货架期， 寿命，简化制造和运输。初步数据强烈表明，这种基于生物材料的， 微粒疫苗系统对于纠正T1 D中的自身免疫应答具有很大的希望。的 迄今为止收集到的压倒性的积极和广泛的数据值得提交这一直接进入第二阶段 SBIR提案，其中OneVax将为OV-01建立可扩展性和稳定性参数，确定 预防糖尿病发作的最小有效剂量，确定其逆转已建立的糖尿病的能力， 并满足FDA要求的临床前安全性评估。最重要的是，战略合作 OneVax和Sid Martin生物技术孵化器，生物医学工程部门， 医学院和佛罗里达大学糖尿病研究所提高了OneVax的能力， 完成预期目标，并使急需的T1 D治疗更接近临床。

Immune-mediated diseases such as type 1 diabetes (T1D), multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosis are reaching epidemic proportions in the US. T1D affects an estimated 1.25 million Americans, with more than 30,000 new patients diagnosed annually, resulting in an estimated $15 billion in health care costs in the US by 2024. T1D is an autoimmune disease characterized by effector T-cell mediated destruction of insulin-producing β-cells, which renders the patient unable to produce insulin and forces the patient to constantly monitor their glucose levels and manually administer insulin for the remainder of their life. Ultimately, glucose metabolism is interrupted, resulting in the development of life-threatening complications such as heart disease and renal failure. Clearly, the cost associated with treatment and care of T1D in the US is significant, both to society and the individual, and a novel therapy is desperately needed to thwart this aberrant autoimmune activity. This is a need that OneVax is committed to fulfilling. The biomedical research community has sought better ways to induce specific immune tolerance for nearly 50 years. Clinical intervention trials using immunomodulatory agents (e.g., anti-CD3) have failed to meet clinical endpoints, despite positive results in phase I/II trials. Moreover, traditional vaccine strategies providing auto-antigen or peptides alone failed to adequately block ongoing beta cell immunity. Thus, a new treatment strategy that is both potent and durable is required to effectively halt the ongoing attack in T1D. Therapeutic vaccination approaches for T1D utilizing dendritic cells (DCs) hold promise to correct antigen- specific autoimmune responses, but current strategies involving exogenous manipulation of DCs are unstable, inefficient and expensive. OneVax has developed a novel in vivo tolerogenic vaccine using GMP-compatible components (designated OV-01) to administer immuno-modulatory factors to phagocytic DCs, the most efficient antigen presenting cell type of the body and key regulator of the immune system. OV-01 is minimally invasive, requires no costly cell isolation and storage, and, due to its stable composition, has an extended shelf- life, simplifying manufacturing and shipping. Preliminary data strongly suggests that this biomaterial-based, microparticle vaccine system holds great promise for correcting autoimmune responses in T1D. The overwhelmingly positive and extensive data collected thus far merits the submission of this Direct-to-Phase II SBIR proposal wherein OneVax will establish scalability and stability parameters for OV-01, determine the minimum effective dose in preventing diabetic onset, determine its capacity for reversing established diabetes, and satisfy the FDA mandated pre-clinical safety assessment. Most importantly, strategic collaborations between OneVax and the Sid Martin Biotechnology Incubator, the Biomedical Engineering Department, the College of Medicine, and the Diabetes Institute at the University of Florida boost the capability of OneVax to complete the desired goals and to bring a much-needed therapy for T1D closer to the clinic.