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Recombinant Hyperimmune Gammaglobulin for Primary Immunodeficiency

重组超免疫丙种球蛋白治疗原发性免疫缺陷

基本信息

批准号：
9139000
负责人：
David Scott Johnson
金额：
$ 75.02万
依托单位：
GIGAGEN, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9139000
关键词：
Address Adult Affect American Antibiotics Antibodies Antibody Repertoire Antigens Bacteria Binding Biochemistry Biological Assay CLIA certified Capital Cells Chronic Chronic lung disease Clinical Cohort Studies Congenital Disorders Cytomegalovirus DNA Library Data Diagnostic Diagnostic tests Doctor of Philosophy Drug Kinetics Europe Exclusion FDA approved Failure Family Flow Cytometry Genomics Hemophilus High Pressure Liquid Chromatography Immune Immune System Diseases Immunocompromised Host Immunologist In Vitro Infection Influenza Intravenous Immunoglobulins Ion Exchange Libraries Light-Chain Immunoglobulins Lung Methods Microfluidics Morbidity - disease rate Outcome Patients Pharmaceutical Preparations Phase Plasma Pneumonia Prophylactic treatment Proteins Recombinants Recurrence Rodent Scientist Sequoia Serum Small Business Innovation Research Grant Specialist Streptococcus Testing Therapeutic Time Toxicology Transplant Recipients United States National Institutes of Health Vaccinated Virus West Nile virus Work X-Linked Agammaglobulinemia antibody libraries combat congenital immunodeficiency improved meetings monomer mortality new technology novel strategies pathogen polyclonal antibody preclinical efficacy product development prophylactic public health relevance response seropositive transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): The Specific Aim of this SBIR direct-to-Phase II project is to develop natural repertoire recombinant intravenous immunoglobulin (rIVIg) "hyperimmunes" against common pathogens for patients with primary immune deficiency (PID). PID is a diverse family of congenital disorders, including common variable immune deficiency (CVID) and X- linked agammaglobulinemia (XLA), which are characterized by significantly reduced antibody titers. Immunologists treat humoral PID with prophylactic intravenous immunoglobulin (IVIg), which is a pool of proteins isolated from the plasma of thousands of donors. Still, 40% of patients suffer recurrent pneumonia, and 36% die from lung failure due to chronic lung disease. Most PID patients with recurrent infections receive prophylactic antibiotics to address chronic infection. Hyperimmunes are plasma-derived gammaglobulins that are enriched for activity against a particular pathogen. Unfortunately, the nine FDA-approved hyperimmunes do not address the pathogens that are most responsible for morbidity and mortality in PID patients. Previously, we developed GigaLink(tm), which uses microfluidics and multiplexed PCR to build massively polyclonal DNA libraries from antibody repertoires, with native heavy and light chain immunoglobulin (Ig) pairing intact. In our preliminary work, we leveraged GigaLink(tm) to produce and characterize hyperimmune influenza rIVIg with >40× enriched binding activity. In this SBIR direct-to-Phase II project, we will add hyperimmunes for two more pathogens of critical importance to PID outcomes, manufacture several test batches of rIVIg, and perform toxicology, pharmacokinetic, and pathogen binding studies. Though PID is the primary clinical indication, these drugs could be used for other kinds of immunocompromised patients, such as transplant recipients. Finally, our therapeutic approach will be useful to combat emerging pathogens, i.e., for West Nile rapid response.