SBIR-STTR Award

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.

Public Health Relevance Statement:
NARRATIVE During drug development, products may contain protein impurities. These proteins may cause unwanted immune responses in the body and can change the safety and effectiveness of the drug. We developed an innovative program called ISPRI-HCP that predicts the likelihood a protein impurity will cause an unwanted immune response. In this study, we propose experiments to evaluate ISPRI-HCP and improve its ability to make predictions.

Project Terms:
Adenoviridae; Adenoviruses; Algorithms; Antibodies; Clinical Treatment Moab; mAbs; monoclonal Abs; Monoclonal Antibodies; Antigenic Determinants; Binding Determinants; Epitopes; immunogen; Antigens; Biological Assay; Assay; Bioassay; Biologic Assays; Biological Products; Biologic Products; Biological Agent; biologics; biopharmaceutical; biotherapeutic agent; Western Blotting; Immunoblotting; Western Immunoblotting; protein blotting; Cell Line; CellLine; Strains Cell Lines; cultured cell line; Cells; Cell Body; High Pressure Liquid Chromatography; HPLC; High Performance Liquid Chromatography; High Speed Liquid Chromatography; Classification; Systematics; DNA; Deoxyribonucleic Acid; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Enzyme-Linked Immunosorbent Assay; ELISA; enzyme linked immunoassay; Human Genome; human whole genome; Goals; Chinese Hamster; In Vitro; Methods; Ovary; Peptides; Production; Proteins; Publishing; Recombinant Proteins; Research; Research Personnel; Investigators; Researchers; Risk; Safety; T-Lymphocyte; T-Cells; thymus derived lymphocyte; Testing; Thrombocytopenia; Thrombopenia; Vaccines; Viral Proteins; Viral Gene Products; Viral Gene Proteins; virus protein; sulfated glycoprotein 2; MAC393 antigen; SGP-2 protein; SGP2; SP 40,40 protein; TRPM-2 protein; TRPM2; X-ray-inducible protein 8; XIP8 protein; apoJ protein; apolipoprotein J; clusterin; complement lysis inhibitor; complement-associated protein SP-40,40 protein; ionizing radiation-induced protein-8; testosterone-repressed prostate message-2 protein; Annexins; Calcimedins; Lipocortins; Measures; CHO Cells; Chinese Hamster Ovary Cell; Process Assessment; Risk Assessment; penton; adenovirus penton protein; SEQ-AN; Sequence Analyses; Sequence Analysis; density; improved; Phase; biologic; Biological; Link; Evaluation; Individual; Licensing; T-Cell Epitopes; T-Lymphocyte Epitopes; Immunological response; host response; immune system response; immunoresponse; Immune response; tool; programs; Investigation; cell type; System; Performance; vaccine development; develop a vaccine; develop vaccines; development of a vaccine; vector vaccine; plasmid vaccine; drug efficacy; Peripheral Blood Mononuclear Cell; PBMC; Speed; novel; Excision; Abscission; Extirpation; Removal; Surgical Removal; resection; drug development; immunogenic; GSTP1 gene; DFN7; FAEES3; Fatty Acid Ethyl Ester Synthase III Gene; GST3; GST3 Gene; GSTP1; GSTPP; Glutathione S-Transferase Pi Gene; Effectiveness; Address; Data; Cellular Assay; cell assay; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Viral Vector; Process; Modification; immunogenicity; vaccine safety; innovate; innovative; innovation; 2-dimensional; two-dimensional; BiP gene; BiP protein; GRP78; Glucose-Regulated Protein, 78-kD; HSPA5; Heat-Shock 70-kD Protein 5; immunoglobulin heavy chain-binding protein; GRP78 gene; flexible; flexibility; high risk group; high risk individual; high risk people; high risk population; experiment; experimental research; experiments; experimental study; web tool; web-based tool; rare syndrome; rare condition; drug safety; pharmaceutical safety; medication safety; in silico; 2019-nCoV vaccine; COVID19 vaccine; SARS-CoV-2 vaccine; SARS-CoV2 vaccine; SARS-coronavirus-2 vaccine; Severe Acute Respiratory Syndrome CoV 2 vaccine; Severe acute respiratory syndrome coronavirus 2 vaccine; corona virus disease 2019 vaccine; coronavirus disease 2019 vaccine; coronavirus disease-19 vaccine; nCoV vaccine; nCoV-19 vaccine; nCoV19 vaccine; vaccine against 2019-nCov; vaccine against SARS-CoV-2; vaccine against SARS-CoV2; vaccine against SARS-coronavirus-2; vaccine against Severe Acute Respiratory Syndrome CoV 2; vaccine against Severe acute respiratory syndrome coronavirus 2; vaccine for novel coronavirus; COVID-19 vaccine; thrombotic; vaccine formulation; manufacture