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Principal Investigator: Connie Schmaljohn
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2023
Award: $42,480,499
Funding agency: National Institute of Allergy and Infectious Diseases
The Integrated Research Facility - Frederick (IRF-Frederick) plays a central role in U.S. Governments high-containment research on emerging infectious diseases. In FY2023, the IRF-Frederick continued support for COVID-19 research and initiated multiple non-COVID-19 research studies.
COVID-19 in vivo research included execution of multiple studies to evaluate the efficacy of therapeutic antibody clinical candidates and defective interfering particles against SARS-CoV-2 in Golden hamsters. COVID-19 hamster studies included analyses of host lung transcriptomes after exposure to 10 different SARS-CoV-2 variants. Efforts have continued in the development of a non-human primate model that recapitulates severe human disease, and an ongoing study involving crab-eating macaques NHP has generated encouraging preliminary results. COVID-19 in vitro research focused on evaluation of potential therapeutic antibodies and human intravenous immunoglobulin for the treatment of SARS-CoV-2 infection.
In FY2023, IRF-Frederick utilized its newly developed high-containment audiometry capability to demonstrate progressive hearing loss in rhesus monkeys exposed to Lassa virus (LASV). This achievement marks the first time that tympanometry and pure tone audiometry have been used in high containment for nonclinical evaluations. Additional LASV in vivo evaluations in Hartley guinea pigs showed 100% survival of LASV-exposed animals treated with a small-molecule therapeutic and, in a separate study, 100% protection conferred by a novel live-attenuated LASV vaccine candidate.
Multiple other in vivo studies were conducted to characterize disease pathogenesis following exposure to high-consequence pathogens. Using serial Magnetic Resonance Imaging (MRI) scans, reactive oxygen species were characterized in ferrets exposed to Ebola virus (EBOV). Positron Emission Tomography and Computed Tomography (PET-CT) serial scans were used to characterize fibrin deposition and coagulopathy in EBOV-exposed Hartley guinea pigs. The efficacy of a vaccine candidate based on a glycoprotein region conserved across multiple filoviruses was evaluated in Marburg-virus exposed cynomolgus macaques. Additionally, in a study involving African Green Monkeys exposed to large-particle aerosolized Nipah virus (NiV)-Bangladesh, clinical signs, immune responses, and pulmonary and neurological changes were characterized.
IRF-Frederick has continued development of its unique advanced medical and pre-clinical imaging capabilities. The imaging team, in collaboration with CIDI partners, has implemented robust analysis workflows to quantify the PET signal in NHP lungs, brain, vasculature, and immune organs and has adapted clinically validated methods to extract quantitative data from morphological and functional brain MRI scans in NHPs. In FY2023, as part of IRF-Fredericks implementation of a multi-year Imaging Equipment Upgrade Plan, two new instruments -- a Mediso Large Field of View Extreme Resolution (LFER) PET/CT scanner; and a Milabs VECTor combined PET, single-photon emission computed tomography (SPECT), CT, and optical imaging system were successfully installed and validated in the Biosafety Level (BSL) 4 laboratory.
IRF-Frederick advanced its organ-chip capability, focusing on the implementation and optimization of an alveolus-on-chip and a small-airway-on-chip protocol within BSL-2 and BSL-4 for SARS-CoV-2 and NiV. Other in vitro projects initiated in FY2023 include utilization of bat stem cells and their progeny to investigate the host-viral pathogen interface, development of an EBOV reporter construct for a project aimed at establishing a transgenic mouse for in vivo virus tracking using optical imaging, and determination of molecular mechanisms of filovirus persistence.
The IRF-Frederick Clinical Study Support Team (CSST) provided diagnostic and research support for 10 clinical protocols, using IRF-Frederick on-site resources and staff deployments to OCONUS sites. CSST staff engaged with OCONUS partners for training and capability-building activities in Guinea, Liberia, and Democratic Republic of the Congo (DRC). Importantly, the CSST assumed responsibility as the primary lead of the laboratory diagnostics functional group for the Pamoja Tulinde Maisha (PALM) 007: Mpox Randomized Clinical Trial.
Eight new projects were initiated in FY2023. IRF-Frederick is engaged in 63 active projects, supporting 79 collaborative partnerships.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Achievement><Achievement Attainment><Active Oxygen><African Green Monkey><Alveolus><Animal Disease Models><Animals><Attenuated><Audiogram><Audiometric Test><Audiometry><Bangladesh><Bats><Belgian Congo><Blood Coagulation Disorders><Brain><Brain Nervous System><Bronchial Alveolus><CAT scan><COVID-19><COVID-19 infection><COVID-19 therapy><COVID-19 treatment><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19><COVID19 infection><COVID19 therapy><COVID19 treatment><COVID19 virus><CT X Ray><CT Xray><CT imaging><CT scan><CV-19><CV19><Cavia><Cell Communication and Signaling><Cell Signaling><Chiroptera><Chlorocebus aethiops><Chlorocebus sabaeus><Clinical><Clinical Protocols><Clinical Research><Clinical Study><CoV-2><CoV2><Coagulation Disorder><Coagulopathy><Collaborations><Computed Tomography><Containment><Crab-Eating Macaque><Crab-Eating Monkey><Cricetinae><Cynomolgus Monkey><Cynomolgus macaque><Data><Defective Hybrids><Defective Interfering Particles><Defective Interfering Viruses><Defective Viruses><Democratic Republic of the Congo><Deposit><Deposition><Development><Diagnostic><Disease><Disorder><EBOV><Ebola virus><Ebola-like Viruses><Emerging Communicable Diseases><Emerging Infectious Diseases><Encephalon><Environment><Equipment><Evaluation><Exposure to><Ferrets><Fibrin><Filoviridae><Filovirus><Frankfurt-Marburg Syndrome Virus><French Guinea><Glycoproteins><Golden Hamsters><Golden Syrian Hamsters><Government><Green Monkey><Guinea><Guinea Pigs><Guinea Pigs Mammals><Hamsters><Hamsters Mammals><Hearing Tests><Human><IGIV><IV Immunoglobulins><IVIG><Image><Immune><Immune globulin IV><Immune response><Immunes><Immunological response><In Vitro><Incomplete Viruses><Infectious Diseases / Laboratory><Infectious Diseases Research><Interdisciplinary Research><Interdisciplinary Study><Intracellular Communication and Signaling><Intravenous Antibodies><Intravenous IG><Intravenous Immune Globulin><Intravenous Immunoglobulins><Laboratories><Lassa fever virus><Lassa virus><Lead><Liberia><Lung><Lung Respiratory System><M fascicularis><M mulatta><M. fascicularis><M. mulatta><MRI Scans><Macaca fascicularis><Macaca mulatta><Magnetic Resonance Imaging Scan><Marburg><Marburg virus><Marburg-like Viruses><Marburgvirus><Medical Imaging><Mesocricetus auratus><Methods><Mission><Modeling><Modern Man><Molecular><Monkey Pox><Monkeypox><Morphology><Multidisciplinary Collaboration><Multidisciplinary Research><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Neurologic><Neurological><Nipah Virus><Organ><Oxygen Radicals><PET><PET Scan><PET imaging><PET/CT><PET/CT scan><PETSCAN><PETT><Pathogenesis><Pb element><Play><Position><Positioning Attribute><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Pro-Oxidants><Progenitor Cells><Protocol><Protocols documentation><Pure-Tone Audiometry><Rad.-PET><Reactive Oxygen Species><Reporter><Research><Research Resources><Research Support><Resolution><Resources><Rhesus Macaque><Rhesus Monkey><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SPECT><SPECT imaging><Scanning><Serial Magnetic Resonance Imaging><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Signal Transduction><Signal Transduction Systems><Signaling><Single-Photon Emission-Computed Radionuclide Tomography><Site><Syrian Hamsters><Therapeutic antibodies><Time><Tomodensitometry><Training><Transgenic Mice><Tympanometry><United States National Institutes of Health><Virulent><Virus><Wuhan coronavirus><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><Zaire><aerosolized><attenuate><attenuates><auditory tests><biological signal transduction><bleeding disorder><brain MR imaging><brain MRI><brain magnetic resonance imaging><catscan><cerebral MR imaging><cerebral MRI><cerebral magnetic resonance imaging><clinical candidate><clotting disorder><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 therapy><coronavirus disease 2019 treatment><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><determine efficacy><developmental><ebolavirus><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><functional group><global gene expression><global transcription profile><hCoV19><hearing assessment><heavy metal Pb><heavy metal lead><host response><human disease><imaging><imaging capabilities><imaging system><immune system response><immunoresponse><in vivo><in vivo evaluation><in vivo testing><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><instrument><mpox><nCoV2><non-contrast CT><non-human primate><noncontrast CT><noncontrast computed tomography><nonhuman primate><novel><optic imaging><optical imaging><particle><pathogen><pathogenic virus><positron emission computed tomography><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><pre-clinical imaging><preclinical imaging><prevent><preventing><progressive hearing loss><pulmonary><randomized, clinical trials><research facility><research study><resolutions><serial MRI><severe acute respiratory syndrome coronavirus 2 therapy><severe acute respiratory syndrome coronavirus 2 treatment><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><single photon emission computed tomography><small molecule therapeutics><social role><stem cells><tool><transcriptome><treat COVID-19><treat COVID19><treat SARS-CoV-2><treat coronavirus disease 2019><treat severe acute respiratory syndrome coronavirus 2><vaccine candidate><vector><viral pathogen><virus pathogen>