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Principal Investigator: Thomas William Geisbert
Organization: UNIVERSITY OF TEXAS MED BR GALVESTON
Fiscal Year: 2024
Award: $4,640,498
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT – Core E (Animal Model Development and Preclinical Evaluation)
Among viruses that cause disease in humans, viral zoonoses within the family Paramyxoviridae and order
Bunyavirales contain pathogens that cause significant lethality. Importantly, the Arenaviridae and Nairoviridae
families contain viruses that cause severe hemorrhagic disease in humans. These viruses include the
arenaviruses Lassa, Machupo, Lujo, and Chapare, and the nairovirus Crimean-Congo hemorrhagic fever virus.
All of these viruses are also included among the World Health Organization’s (WHO) List of Priority Pathogens.
Within the Paramyxovirdae, the zoonotic henipaviruses Hendra virus and Nipah virus (NiV) are also on the WHO
Priority Pathogens list. Notably, these henipaviruses stand out for their impressive lethality with case fatality
rates averaging about 75%. Significantly, there is evidence of multiple rounds of person-to-person transmission
of NiV. All of these RNA viruses pose threats to global public health due to the absence of approved vaccines or
therapeutics. There is a clear unmet need for countermeasures to address the threat of natural outbreaks,
epidemics, or deliberate release. The Paramyxoviridae and Bunyavirales Vaccines and Antibodies Center
(PABVAX) is a well-integrated consortium conducting a set of discovery and translational research programs
composed of a Data Management Core, three Scientific Cores, and five Research Projects (RPs). The
synergistic activities of PABVAX partners will be focused on developing novel vaccines, treatments, and tools to
foster pandemic preparedness. Federal law requires that the arenaviruses, nairoviruses, and henipaviruses used
in the PABVAX Center be handled in an approved Biosafety Level (BSL)-4 containment laboratory. Core E
provides an approved BSL-4 facility and a trained and highly experienced team of BSL-4 investigators and staff
to perform studies that support RP1, RP2, RP4, RP5, Core C, and Core D. Core E will perform well-documented
animal efficacy studies based on a quality system approach that will be supported by Core A with all data
generated managed by Core B. The services provided by Core E will include 1) a secure repository of well
characterized seed stocks of BSL-4 arenaviruses, nairoviruses, and henipaviruses 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 strains or variants of henipaviruses,
arenaviruses, and nairoviruses to fill gaps as needed; 6) generation of tools including immune reagents and
inactivated samples from animals for distribution to RPs, Cores, and other ReVAMPP Centers; 7) virus challenge,
vaccination, treatment, and collection of samples from animals; 8) technical expertise and equipment to conduct
clinical pathological, immunological, and virological analysis of samples and to perform necropsies in BSL-4
containment; 9) histopathological analysis of tissues collected from animals infected with BSL-4 viruses; and 10)
quality systems management of all records and data generated from animal studies.
Terms: <Address><Animal Husbandries><Animal Husbandry><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Arenaviridae><Arenavirus><Arenavirus group><Assay><Autopsy><BSL-4 facility><BSL4 facility><Bioassay><Biological Assay><Bleeding><Blood Sample><Blood specimen><Body Tissues><Bolivian Hemorrhagic Fever Virus><Bunyavirales><Case Fatality Rates><Chapare><Chapare Virus><Clinical><Clinical Chemistry><Clinical Pathology><Collaborations><Congo Virus><Congo hemorrhagic fever virus><Containment><Crimean Hemorrhagic Fever Virus><Crimean-Congo Hemorrhagic Fever Virus><Crimean-Congo hemorrhagic fever orthonairovirus><Data><Development><Disease><Disease Outbreaks><Disorder><Endotoxins><Eperythrozoon><Epidemic><Equine Morbillivirus><Equipment><Family><Fostering><Generations><Genomics><Haemobartonella><Hematology><Hemorrhage><Hendra Virus><Hendra henipavirus><Henipavirus><History><Housing><Human><Human Resources><IACUC><Immune><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Immunology><In Vitro><Infection><Institutional Animal Care and Use Committee><Investigators><Laboratories><Langya><Lassa><Laws><Lujo><Lujo virus><Machupo><Machupo virus><Manpower><Modeling><Modern Man><Monitor><Mycoplasma><Nairovirus><Nipah Virus><Nipah henipavirus><Outbreaks><Paramyxoviridae><Paramyxovirus><Pathologic><Pathology><Periodicals><Persons><Plaque Assay><Protocol><Protocols documentation><Public Health><R-Series Research Projects><R01 Mechanism><R01 Program><RNA Viruses><RT-PCR><RTPCR><Reagent><Recombinants><Recording of previous events><Records><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Resources><Reverse Transcriptase Polymerase Chain Reaction><Sampling><Secure><Services><System><Technical Expertise><Testing><Therapeutic><Tissue Sample><Tissues><Training><Translational Research Enterprise><Transmission><Vaccination><Vaccines><Variant><Variation><Viral><Viral Activity><Viral Burden><Viral Function><Viral Load><Viral Load result><Viral Physiology><Virus><World Health Organization><Zoonoses><Zoonotic><Zoonotic Infection><animal efficacy><animal model development><animal tissue><biosafety level 4 facility><blood loss><data management><depository><design><designing><developmental><efficacy study><evaluate vaccines><experience><histories><human disease><in vitro Assay><model of animal><multiplex assay><necropsy><new vaccines><next generation vaccines><novel vaccines><pandemic disease preparedness><pandemic planning><pandemic preparedness><pandemic readiness><pathogen><periodic><periodical><personnel><postmortem><pre-clinical evaluation><preclinical evaluation><priority pathogen><recombinant virus><repository><reverse genetics><reverse transcriptase PCR><sample collection><specimen collection><sterility testing><technical skills><tool><transcriptomics><translation research enterprise><translational research program><transmission process><vaccine evaluation><vaccine screening><vaccine testing><virology>