Integrated Research Facility at Fort Detrick

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

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.