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Principal Investigator: Thomas William Geisbert
Organization: UNIVERSITY OF WASHINGTON
Fiscal Year: 2024
Award: $5,867,641
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY – CORE D: ANIMAL MODELS AND VACCINE EVALUATION
Among viruses that cause disease in humans viral zoonoses within the family Paramyxoviridae and order
Bunyavirales contain pathogens that cause significant lethality. Importantly, within the Paramyxovirdae the
zoonotic henipavirus Hendra virus (HeV) is on the World Health Organizations (WHO) Priority Pathogens list.
Notably, henipaviruses stand out for their impressive lethality with case fatality rates averaging about 75%. The
Arenaviridae and Phelboviridae families contain viruses that cause severe hemorrhagic disease in humans.
These viruses include the arenaviruses Lassa virus (LASV) and Junin virus (JUNV) and the phleboviruses Rift
Valley fever virus (RVFV) and severe fever with thrombocytopenia syndrome virus (SFTSV). LASV and RVFV
are also included among the WHO List of Priority Pathogens and pose threats to global public health due to the
absence of approved vaccines or therapeutics. There is a clear unmet need for medical countermeasures to
combat the threat of natural outbreaks, epidemics, or deliberate release. The synergistic activities of the Center
partners will be focused on developing novel vaccines, treatments, and tools to support pandemic
preparedness. Federal law requires that the paramyxoviruses, arenaviruses, and phleboviruses used in the
Center be handled in approved Biosafety Level (BSL)-3 and BSL-4 containment laboratories. Core D provides
approved BSL-3/ABSL-3 and BSL-4/ABSL-4 facilities and a trained and highly experienced team of BSL-3 and
BSL-4 investigators and staff to perform studies that support Project 2 - 5. The services provided by Core D will
include 1) a secure repository of well characterized seed stocks of BSL-3 and BSL-4 paramyxoviruses,
arenaviruses, and phleboviruses and know-how to rescue synthetic infectious clones (e.g. Ghana virus, GhV
for this U19); 2) in vitro antiviral activity assays; 3) procurement of UTMB IACUC approval of animal protocols;
4) procurement, housing, and husbandry of animals; 5); development and/or optimization of animal models for
GhV, Sosuga virus (SOSV) and JUNV to fill gaps where models are needed; 6) virus challenge, treatment, and
collection of samples from animals; 7) technical expertise and equipment to conduct clinical pathological,
immunological, and virological analysis of samples and to perform necropsies in BSL-3 and BLS-4
containment; 8) histopathological analysis of tissues collected from animals infected with BSL-3 and BSL-4
viruses; and 9) quality systems management of all records and data collected from animal studies. The Animal
Models and Vaccine Evaluation Scientific Core (Core D) provides BSL-3 and BSL-4 resources and expertise
for Projects 2 – 5. The goal of Core D is to work closely with Research Project and Scientific Core Leaders and
staff, the Scientific Advisory Board, and NIAID to advance the development of countermeasures against
Paramyxoviridae and Bunyaviridae.
Terms: <Advanced Development><Animal Husbandries><Animal Husbandry><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody Response><Antibody Therapy><Arenaviridae><Arenavirus><Arenavirus group><Argentine hemorrhagic fever virus><Argentinian Hemorrhagic Fever Virus><Assay><Autopsy><Bioassay><Biological Assay><Bleeding><Blood Sample><Blood specimen><Body Tissues><Bunyavirales><Bunyaviridae><Case Fatality Rates><Cell Body><Cells><Clinical><Clinical Chemistry><Clinical Pathology><Clinical Treatment Moab><Containment><Data><Development><Disease><Disease Outbreaks><Disorder><Endotoxins><Eperythrozoon><Epidemic><Equine Morbillivirus><Equipment><Family><Genomics><Genus Phlebovirus><Ghana><Goals><Gold Coast><Haemobartonella><Hematology><Hemorrhage><Hendra Virus><Hendra henipavirus><Henipavirus><History><Housing><Human><Human Resources><IACUC><Immune response><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><In Vitro><Institutional Animal Care and Use Committee><Investigators><Junin><Junin virus><Laboratories><Lassa fever virus><Lassa virus><Laws><Machine Learning><Manpower><Modeling><Modern Man><Monitor><Monoclonal Antibodies><Mycoplasma><NIAID><National Institute of Allergy and Infectious Disease><Neutralization Tests><Outbreaks><Paramyxoviridae><Paramyxovirus><Pathologic><Pathology><Periodicals><Phlebovirus><Plaque Assay><Protocol><Protocols documentation><Public Health><R-Series Research Projects><R01 Mechanism><R01 Program><RT-PCR><RTPCR><Recording of previous events><Records><Reporter><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Resources><Reverse Transcriptase Polymerase Chain Reaction><Rift Valley fever virus><Sampling><Scientific Evaluation><Secure><Services><Severe Fever and Thrombocytopenia Syndrome Virus><Severe Fever with Thrombocytopenia Syndrome Virus><Severe Fever with Thrombocytopenia virus><System><Technical Expertise><Testing><Therapeutic><Tissue Sample><Tissues><Training><Vaccination><Vaccines><Viral><Viral Activity><Viral Burden><Viral Function><Viral Load><Viral Load result><Viral Physiology><Virus><Work><World Health Organization><Zoonoses><Zoonotic><Zoonotic Infection><animal tissue><antibody based therapies><antibody neutralization test><antibody treatment><antibody-based therapeutics><antibody-based treatment><blood loss><combat><data management><depository><design><designing><developmental><evaluate vaccines><experience><histories><host response><immune system response><immunoresponse><in vitro Assay><mAbs><machine based learning><medical countermeasure><model of animal><monoclonal Abs><necropsy><neutralizing antibody><new vaccines><next generation vaccines><novel vaccines><pandemic disease preparedness><pandemic planning><pandemic preparedness><pandemic readiness><pathogen><periodic><periodical><personnel><postmortem><priority pathogen><prototype><repository><reverse transcriptase PCR><sample collection><sandfly fever virus group><specimen collection><sterility testing><technical skills><tool><vaccine antibodies><vaccine efficacy><vaccine evaluation><vaccine induced antibodies><vaccine response><vaccine responsiveness><vaccine screening><vaccine testing><vaccine-induced antibodies><vaccine-induced response><virology>