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(T1D)、多发性硬化症、类风湿性关节炎和 系统性红斑狼疮在美国正达到流行的程度。T1D影响估计为1.25 100万美国人，每年有30,000多名新患者被诊断出来，估计产生了15美元 到2024年，美国的医疗成本将达到10亿美元。T1D是一种以效应性T细胞为特征的自身免疫性疾病 介导的产生胰岛素的β细胞的破坏，使患者无法产生胰岛素和 强制患者持续监测血糖水平，并在剩余时间手动注射胰岛素 他们生命的一部分。最终，葡萄糖代谢中断，导致危及生命的 心脏病和肾功能衰竭等并发症。显然，与治疗和护理有关的费用 在美国，T1D对社会和个人都具有重要意义，迫切需要一种新的疗法来治疗 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(例如，抗CD3)的临床干预试验失败 达到临床终点，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多肽并不能充分阻止正在进行的β细胞免疫。因此，一个新的 需要既有效又持久的治疗策略来有效阻止T1D正在进行的攻击。 利用树突状细胞(DC)的T1D治疗性疫苗接种方法有望纠正抗原- 特异性自身免疫反应，但目前涉及外源性操纵DC的策略不稳定， 效率低下，价格昂贵。OneVax已经开发出一种新的体内耐受疫苗，使用与GMP兼容的 对吞噬DC施加免疫调节因子的成分(命名为OV-01)，最 体内高效的抗原提呈细胞类型，是免疫系统的关键调节因子。OV-01是最低的 侵入性，不需要昂贵的细胞分离和存储，并且由于其稳定的组成，具有扩展的货架- 生活，简化制造和运输。初步数据有力地表明，这种基于生物材料的 微粒疫苗系统在纠正T1D的自身免疫反应方面具有很大的前景。这个 到目前为止收集的绝大多数积极和广泛的数据值得提交这份直接到第二阶段的报告 SBIR提案，其中OneVax将建立OV-01的可扩展性和稳定性参数，确定 预防糖尿病发病的最小有效剂量，确定其逆转已确立的糖尿病的能力， 并满足FDA规定的临床前安全性评估。最重要的是，战略协作 在OneVax和Sid Martin生物技术孵化器之间，生物医学工程部， 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，并将急需的T1D疗法带到离诊所更近的地方。

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.