Document text
Principal Investigator: Thomas William Geisbert
Organization: UNIVERSITY OF TEXAS MED BR GALVESTON
Fiscal Year: 2020
Award: $2,655,768
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT – BSL-4 Evaluation Core (Core B)
Among viruses that cause disease in humans the filoviruses, Ebolavirus and Marburgvirus, stand out for their
impressive lethality. These viruses are the most deadly human pathogens known to man with reported case
fatality rates of up to 90%. The recent unprecedented 2013-16 epidemic of Zaire ebolavirus in West Africa
resulting in over 28,000 cases and 11,000 deaths demonstrates the ability of filoviruses to emerge in new
regions. In addition to natural outbreaks, Ebolavirus and Marburgvirus are known to have been the subjects of
former biological weapons programs and have the potential for deliberate misuse. Currently, there are no filovirus
vaccines or treatments approved for human use. For these reasons Ebolavirus and Marburgvirus have recently
been included as only two of eleven human pathogens on the new US Department of Health and Human Services
(HHS) Tier 1 list of Category A select agents. All three of the Research Projects within the Center focus on
developing broad spectrum rapid acting vaccines or therapeutics against all medically relevant variants and
species of filoviruses. RP1 employs recombinant vesicular stomatitis virus (VSV)-based rapid acting vaccines,
RP2 focuses on fully human anti-filovirus monoclonal antibodies, and RP3 focuses on anti-filovirus small
interfering RNAs, small molecule antivirals, and combination treatments. A unique aspect of this Center is that
these approaches represent a very small cohort of medical countermeasures that have shown the ability to
provide complete single injection vaccination or therapeutic protection of nonhuman primates (NHPs) against
filoviruses. All three Center Research Projects require that countermeasures be evaluated in animals against
infectious filoviruses. Federal law requires that filoviruses be handled in an approved Biosafety Level (BSL)-4
containment laboratory. Core B 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-RP3. Core B will perform “well-documented”
NHP efficacy studies and also “pivotal” NHP studies that will be conducted in accordance with a GLP-based
quality agreement and will be supported by a dedicated quality assurance/quality control team. The services
provided by Core B will include 1) a secure repository of well characterized seed stocks of BSL-4 filoviruses; 2)
in vitro antiviral activity assays; 3) procurement of UTMB IACUC approval of animal protocols; 3) procurement,
housing, and husbandry of animals; 5) virus challenge, treatment, and collection of samples from animals; 6)
technical expertise and equipment to conduct clinical pathological and virological analysis of samples and to
perform necropsies in BLS-4 containment; 7) histopathological analysis of tissues collected from animals infected
with filoviruses; and 8) quality systems management of all records and data collected from NHP studies.
Terms: <Africa><Agreement><Animal Husbandries><Animal Husbandry><Animals><Antiviral Agents><Antiviral Drugs><Antivirals><Assay><Autopsy><BDBV><BSL-4 facility><BSL4 facility><Bioassay><Biologic Assays><Biological Assay><Blood Sample><Blood specimen><Body Tissues><Bundibugyo ebola virus><Bundibugyo ebolavirus><Bundibugyo virus><Case Fatality Rates><Case Study><Categories><Cessation of life><Clinical><Clinical Chemistry><Clinical Pathology><Clinical Treatment Moab><Containment><Cyclicity><Data><Death><Department of Health and Human Services><Disease><Disease Outbreaks><Disorder><EBOV><Ebola virus><Endotoxins><Eperythrozoon><Epidemic><Equipment><Evaluation><Filoviridae><Filovirus><Frankfurt-Marburg Syndrome Virus><Genomics><Haemobartonella><Hematology><History><Housing><Human><Human Resources><IACUC><In Vitro><Injections><Institutional Animal Care and Use Committee><Investigators><Laboratories><Laws><Manpower><Marburg><Marburg virus><Medical><Modern Man><Monitor><Monoclonal Antibodies><Mycoplasma><Outbreaks><Pathologic><Pathology><Periodicity><Plant Embryos><Plant Zygotes><Plaque Assay><Protocol><Protocols documentation><Quality Control><R-Series Research Projects><R01 Mechanism><R01 Program><RT-PCR><RTPCR><Recombinants><Recording of previous events><Records><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Resources><Reverse Transcriptase Polymerase Chain Reaction><Rhythmicity><SUDV><Sampling><Secure><Seeds><Services><Short interfering RNA><Small Interfering RNA><Sudan Ebola virus><Sudan ebolavirus><Sudan virus><System><Technical Expertise><Testing><Therapeutic><Tissue Sample><Tissues><Training><United States Department of Health and Human Services><United States Dept. of Health and Human Services><VSV><Vaccination><Vaccines><Variant><Variation><Vesicular Stomatitis Virus><Vesicular stomatitis Indiana virus><Viral Burden><Viral Diseases><Viral Load><Viral Load result><Virus><Virus Diseases><ZEBOV><Zaire Ebola virus><Zaire ebolavirus><animal tissue><anti-viral agents><anti-viral drugs><anti-virals><base><biological weapon><biosafety level 4 facility><bioweapon><case report><cohort><depository><design><designing><ebolavirus><efficacy study><experience><human pathogen><in vitro Assay><mAbs><man><man's><medical countermeasure><necropsy><non-human primate><nonhuman primate><personnel><postmortem><programs><quality assurance><repository><reverse transcriptase PCR><sample collection><seed><siRNA><small molecule><specimen collection><sterility testing><technical skills><viral infection><virology><virus infection><virus-induced disease>