Validation and Improvement of ISPRI-HCP: An Innovative Platform for Immunogenicity Risk Assessment of Process-related Protein Impurities

ISPRI-HCP 的验证和改进：工艺相关蛋白质杂质免疫原性风险评估的创新平台

• 批准号: 10603538
• 负责人: Kirk Donald Haltaufderhyde
• 金额: $ 29.99万
• 依托单位: EPIVAX, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603538
• 关键词: Address; Adenoviruses; Algorithms; Annexins; Antibodies; Antigens; Biological; Biological Assay; Biological Products; COVID-19 vaccine; Cell Line; Cells; Cellular Assay; Chinese Hamster; Chinese Hamster Ovary Cell; Classification; DNA; Data; Effectiveness; Enzyme-Linked Immunosorbent Assay; Epitopes; Evaluation; Excision; GRP78 gene; GSTP1 gene; Goals; High Pressure Liquid Chromatography; Human Genome; Immune response; In Vitro; Individual; Investigation; Licensing; Link; Measures; Methods; Modification; Monoclonal Antibodies; Ovary; Peptides; Performance; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phase; Process; Process Assessment; Production; Proteins; Publishing; Recombinant Proteins; Research; Research Personnel; Risk; Risk Assessment; Safety; Sequence Analysis; Small Business Innovation Research Grant; Speed; System; T-Lymphocyte; T-Lymphocyte Epitopes; Testing; Thrombocytopenia; Vaccines; Validation; Viral Proteins; Viral Vector; Western Blotting; adenovirus penton protein; cell type; density; drug development; drug efficacy; experimental study; flexibility; high risk population; immunogenic; immunogenicity; improved; in silico; innovation; manufacture; medication safety; novel; programs; rare condition; sulfated glycoprotein 2; thrombotic; tool; two-dimensional; vaccine development; vaccine formulation; vaccine safety; vector vaccine; web-based tool

ABSTRACT The identification and removal of process-related protein impurities (PRPI) from biologic products is a critical step in drug development. Despite recent improvements in the purification and processing of biologics, the presence of immunogenic PRPI continue to raise concerns about drug safety and efficacy. We propose an innovative approach for assessing immunogenicity risk of PRPI using our existing ISPRI-HCP platform. ISPRI- HCP stands apart from conventional methods by utilizing a T cell approach based on the T cell epitope count and density. We hypothesize that ISPRI-HCP can accurately classify candidate PRPI impurities according to their immunogenicity risk. To test this hypothesis, we will determine the T cell immunogenicity of 8 frequently found PRPI from Chinese Hamster Ovary (CHO) cell expression systems and 5 PRPI from adenoviral vaccines. The selected PRPI classified by ISPRI-HCP cover a wide range of immunogenicity risk. Peptide pools comprised of T cell epitopes of the selected proteins will be prepared and tested for their ability to induce antigen-specific INF-g secreting T cells in assays using peripheral blood mononuclear cells (PBMCs). The overall goal of this study is to provide proof-of-concept and further improve ISPRI-HCP as a platform for predicting the immunogenicity risk of PRPI.

抽象的 识别并去除生物制品中与工艺相关的蛋白质杂质 (PRPI) 至关重要 药物开发的一步。尽管最近在生物制品的纯化和加工方面取得了进步，但 免疫原性 PRPI 的存在继续引起人们对药物安全性和有效性的担忧。我们提出一个 使用我们现有的 ISPRI-HCP 平台评估 PRPI 免疫原性风险的创新方法。 ISPRI- HCP 与传统方法不同，它利用基于 T 细胞表位计数的 T 细胞方法 和密度。我们假设 ISPRI-HCP 可以根据以下条件准确分类候选 PRPI 杂质： 他们的免疫原性风险。为了验证这一假设，我们将经常测定 8 种 T 细胞的免疫原性 从中国仓鼠卵巢 (CHO) 细胞表达系统中发现了 PRPI，并从腺病毒疫苗中发现了 5 个 PRPI。 由 ISPRI-HCP 分类的所选 PRPI 涵盖了广泛的免疫原性风险。肽池组成 将制备所选蛋白质的 T 细胞表位并测试其诱导抗原特异性的能力 在使用外周血单核细胞 (PBMC) 的检测中分泌 INF-g 的 T 细胞。本次活动的总体目标 研究的目的是提供概念验证并进一步改进 ISPRI-HCP 作为预测的平台 PRPI 的免疫原性风险。