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Novel Therapy for SARS-CoV-2 Virus Infection and Pathogenesis by Aerosol Delivery of Monoclonal Antibodies

通过单克隆抗体气溶胶递送治疗 SARS-CoV-2 病毒感染和发病机制的新疗法

基本信息

批准号：
10400511
负责人：
Peter Gordon Barr-Gillespie
金额：
$ 49.96万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10400511
关键词：
2019-nCoV Aerosols Animal Housing Animals Antibodies Antibody Therapy Antibody titer measurement Autopsy Basic Science Biomedical Research Blood Breeding COVID-19 COVID-19 mortality COVID-19 pandemic COVID-19 prevention COVID-19 therapeutics COVID-19 treatment Caring Clinical Clinical Trials Collaborations Congresses Containment Core Grant Coronavirus Coronavirus Infections Development Devices Disease Dose Effectiveness Equipment Evaluation Failure Freeze Drying Funding Goals Grant Harvest Health Histology Home Hour Human Immunoglobulin A Immunoglobulin M Immunologics Immunology Immunotherapeutic agent Individual Infant Infection Infusion procedures Inhalation Inhalation Drug Administration Intraperitoneal Injections Intravenous Japanese Monkey Knowledge Laboratory Animals Link Lung Macaca Macaca fascicularis Macaca mulatta Medical Methods Mission Modeling Monoclonal Antibodies Mucous Membrane Mus Nebulizer Nose Oregon Outcome Papio anubis Particle Size Pathogenesis Pathology Patients Prevention Primates Process Protocols documentation Quality of life Rattus Research Resistance Respiratory Syncytial Virus Infections Respiratory System Respiratory syncytial virus Risk SARS-CoV-2 antibody SARS-CoV-2 infection SARS-CoV-2 spike protein SARS-CoV-2 variant Safety Saimiri Sampling Savings Site Social Distance Source Specificity Standardization Streptococcus pneumoniae Surface Symptoms Testing Therapy Evaluation Time Tissues Topical application United States National Institutes of Health Vaccines Variant Viral Pathogenesis Viremia Virus Virus Diseases Virus Shedding adaptive immunity advanced disease aerosolized convalescent plasma coronavirus vaccine cost cost effective experimental study human disease human monoclonal antibodies immunoprophylaxis improved individual variation influenza infection nanobodies nasal swab neutralizing monoclonal antibodies nonhuman primate novel novel strategies novel therapeutics oropharyngeal swab pandemic disease parent grant passive antibodies passive immunoprophylaxis polyclonal antibody prevent programs vaccine evaluation viral RNA virology

项目摘要

PROJECT SUMMARY The Oregon National Primate Research Center (ONPRC) is one of seven National Primate Research Centers (NPRCs) established by Congress in the 1960s. The NPRCs are sponsored by the NIH Office of the Director, and serve the nation's biomedical research needs in a unique and essential fashion through cost-effective provision of NHPs and related scientific expertise, specialized facilities, and equipment to federally funded studies of NHPs that comprise a vital translational link between basic research and human applications. The mission of the ONPRC is to improve human health and the quality of life through NHP research programs that advance our knowledge of the causes of human diseases and that develop effective preventions, treatments, and cures. The Oregon National Primate Research Center (ONPRC) P51 Core Grant (P51-OD011092) supports a colony of approximately 4900 breeding and research nonhuman primates (NHPs), including rhesus macaques of Indian origin, Japanese macaques, cynomolgus macaques, Hamadrayas and olive baboons, and a small number of squirrel monkeys. Rhesus and Japanese macaques are bred at the Center. Other species are imported from domestic sources to fulfill project specific research needs. In this supplement proposal to the parent grant, we will test the hypotheses that: 1) When given prior to challenge, inhaled, aerosolized neutralizing monoclonal antibodies can prevent or mitigate SARS-CoV-2 infection in rhesus macaques; and 2) Inhaled neutralizing monoclonals can reduce viremia and prevent pathogenesis when given after challenge. To test these hypotheses, we will test a cocktail of human mAbs with potent and broad SARS-CoV2-neutralizing activity for their effectiveness in pre-exposure protection and/or limitation of viral shedding following aerosolization and administration by inhalation prior to intranasal/intratracheal challenge with SARS-CoV-2. Animals will be followed for virological and immunological outcomes and pathology using standard protocols developed by the Coronavirus Vaccines and Therapy Evaluation Network. At necropsy, tissues will be harvested and processed for virus quantification and histology. For post-exposure studies, macaques will be infected with SARS-CoV-2, and treated one day later with the same cocktail of human SARS-CoV-2 mAbs, comparing aerosol and intravenous delivery at various doses. These proof-of-principle experiments will pave the way for post-exposure aerosol treatments with potent antibodies and nanobodies toward the goal of reducing COVID-19 disease. Our findings will expand the utility of the nonhuman primate model for SARS-CoV-2 and will support the discovery of novel therapeutics for COVID-19, thereby fulfilling the primary purpose of the P51 grant.

项目总结