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Principal Investigator: Peter Gordon Barr-Gillespie
Organization: OREGON HEALTH & SCIENCE UNIVERSITY
Fiscal Year: 2021
Award: $499,631
Funding agency: NIH Office of the Director
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.
Terms: <19S Gamma Globulin><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Aerosols><Animal Housing><Animals><Antibodies><Antibody Therapy><Antibody titer measurement><Autopsy><Basic Research><Basic Science><Biomedical Research><Blood><Blood Reticuloendothelial System><Body Tissues><Breeding><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 S protein><COVID-19 antibody><COVID-19 associated death><COVID-19 associated fatality><COVID-19 associated mortality><COVID-19 crisis><COVID-19 death><COVID-19 epidemic><COVID-19 fatality><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 induced death><COVID-19 induced fatality><COVID-19 induced mortality><COVID-19 infection><COVID-19 mortality><COVID-19 pandemic><COVID-19 prevention><COVID-19 public health crisis><COVID-19 related death><COVID-19 related fatality><COVID-19 related mortality><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 therapeutics><COVID-19 therapy><COVID-19 treatment><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID19><COVID19 S protein><COVID19 associated death><COVID19 associated fatality><COVID19 associated mortality><COVID19 crisis><COVID19 death><COVID19 epidemic><COVID19 fatality><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 infection><COVID19 mortality><COVID19 pandemic><COVID19 prevention><COVID19 public health crisis><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 therapeutics><COVID19 therapy><COVID19 treatment><COVID19 virus><CV-19><CV19><Caring><Clinical><Clinical Treatment Moab><Clinical Trials><CoV-2><CoV2><Collaborations><Common Rat Strains><Congresses><Containment><Core Grant><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><Crab-Eating Macaque><Crab-Eating Monkey><Cynomolgus Monkey><Cynomolgus macaque><D pneumoniae><D. pneumoniae><Development><Devices><Diplococcus pneumoniae><Disease><Disorder><Dose><Effectiveness><Equipment><Evaluation><Failure><Freeze Drying><Freeze Dryings><Funding><Goals><Grant><Harvest><Health><Histology><Home><Hour><Hu-mABs><Human><IP injection><IgA><IgM><Immunochemical Immunologic><Immunoglobulin A><Immunoglobulin M><Immunologic><Immunological><Immunologically><Immunologics><Immunology><Immunotherapeutic agent><Individual><Infant><Infection><Infusion><Infusion procedures><Inhalation><Inhalation Administration><Inhalation Drug Administration><Inhalation Route of Drug Administration><Inhaling><Intraperitoneal Injections><Intravenous><Japanese Monkey><Japanese macaque><Knowledge><Laboratory Animals><Link><Lung><Lung 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