Fully human recombinant therapeutic anti-vaccinia virus polyclonal antibody

生物恐怖主义的威胁使天花再次成为对公共健康的潜在威胁，从而 确定了对新的治疗或预防措施的需要。使用的天花疫苗 全球疫苗接种计划与罕见但严重的不良反应有关，其中一些是致命的 防止大规模接种疫苗。这一应用描述了一种重组的临床前开发 用作预防或治疗天花的人类多克隆天花抗体，以及 相关正痘病毒。一种特异而有效的抗正痘病毒多克隆抗体将使 预防天花的对策，取代血源性牛痘免疫球蛋白(VIG)，提供 显著改善了安全状况和产品供应，减少了注射量，并使 注射，包括为卫生保健人员开发可自我管理的注射装置和 士兵们。这一重组多克隆抗体产品将反映出该病毒的多样性、亲和力和特异性 自然的人类免疫反应。因为多克隆抗体是针对多个表位的 蛋白质，这种抗体有望具有很强的效力。本项目的总体目标是使 提交一份IND。 将在GMP下产生多克隆主细胞系，并验证其遗传稳定性和 不孕不育。该电池线将用于生产工艺的开发和扩大。A下游 将建立抗体提纯、配方和填充-整理的流程。流程和程序 已在Symphogen的更高级项目中建立，用于生产治疗性多克隆 抗体是可以适应的。 该多克隆抗体的生物活性将在痘苗病损尾鼠模型和 致命的小鼠模型。如果最初的模型显示有效，抗病毒活性也将被测试。 猴痘病毒的复制模型与与天花病毒蛋白结合的研究同时进行。加在一起， 这些数据可能为多克隆抗体同时发挥治疗和预防作用提供证据。 对抗正痘病毒。从概念研究和生产论证中收集的结果和 提纯过程将使IND能够填充。

The threat of bioterrorism has reintroduced smallpox as a potential threat to public health and thereby established a need for novel treatments or prophylactic measures. The smallpox vaccine used during the worldwide vaccination program is associated with rare but serious adverse reactions, some fatal, thereby preventing mass vaccination. This application describes the pre-clinical development of a recombinant human polyclonal smallpox antibody to be used as a prophylactic or therapeutic agent against smallpox, and related orthopoxviruses. A specific and potent anti-orthopoxvirus polyclonal antibody will, enable countermeasure against smallpox, substitute the blood-derived vaccinia immunoglubulin (VIG), providing a significantly improved safety profile and product supply, decreased injection volumes, and easier route of injection, including the development of self-manageable injection devices for health care personnel and soldiers. This recombinant polyclonal antibody product will mirror the diversity, affinity and specificity of the natural human immune response. Because the polyclonal antibody is directed against multiple epitopes and proteins, the antibody is expected to be highly potent. The overall goal of the present project is to enable the filing of an IND. A polyclonal master cell line will be generated under GMP and validated with respect to genetic stability and sterility. The cell line will be used during development of a production process and scale-up. A downstream process for antibody purification, formulation, and fill-finish will be established. Processes and procedures already established in more advanced projects at Symphogen for production of therapeutic polyclonal antibodies can be adapted. The biological activity of the polyclonal antibody will be tested in the vaccinia lesion tail mouse model and a lethal mouse model. If the initial models show efficacy, the antiviral activity will also be assayed against monkeypox virus in a replication model in parallel with studies of binding to variola virus proteins. Combined, the data may provide evidence that the polyclonal antibody exerts both therapeutic and prophylactic activity against orthopoxviruses. The collected results from the proof of concept studies and production and purification processes will enable the filling of an IND.