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Principal Investigator: Courtney Cohen
Organization: ALBERT EINSTEIN COLLEGE OF MEDICINE
Fiscal Year: 2024
Award: $3,193,054
Funding agency: National Institute of Allergy and Infectious Diseases
In vivo efficacy testing is essential for the down-selection, evaluation, and development of potent
and effective medical countermeasures (MCMs), especially given that many aspects of viral
replication and pathogenesis cannot be faithfully recapitulated in vitro. Core D is responsible for
providing PROVIDENT Research Projects 1, 2, 3, and 4 animal model testing support required
for the validation of newly identified host factors (Project 1; P1) and novel MCMs (Project 2-4;
P2-4) against hantaviruses, nairoviruses, and paramyxoviruses. First, we will test in vitro down-
selected candidates against family-specific prototype viruses, Andes virus (ANDV), Crimean
Congo Hemorrhagic fever virus (CCHFV), and Menangle virus (MenPV), respectively. To meet
these objectives, animal models will be developed when unavailable and used in conjunction with
widely accepted models. Following, PROVIDENT products will be sprint tested against outgroup
hanta-, nairo-, and paramyxo-viruses, Sin Nombre virus (SNV) or Hantaan virus (HTNV), Hazara
virus (HAZV), and Nipah virus (NiV), respectively. Core D will also support the development of
animal-based tools, including genome-edited murine and Syrian hamsters that will be used to
generate novel rodent models of disease and interrogate fundamental viral-host factor
interactions. In collaboration with P2, P3, Core C, and Core E, Core D will also assist in the
generation of camelid variable heavy chain only antibodies (VHHs), through alpaca immunizations
with RNA/NLP and protein immunogens. These nanobodies will serve as important tools to
identify critical functional surfaces in viral proteins that can inform immunogen engineering. In
addition to animal model development and rodent efficacy studies, Core D will support
immunogenicity testing in non-human primates to assess lead mRNA vaccine candidates and
provide supporting data for pre-clinical or phase I trials. In sum, the support and scientific rigor
provided by Core D will enable PROVIDENT to identify, develop, and test robust MCM against
hantaviruses, nairoviruses, and paramyxoviruses in service of the grand goal of developing
comprehensive vaccine and therapeutic antibody blueprints against these emerging RNA viruses.
Terms: <Alpaca><Andes Virus><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antigens><Blood Vessels><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Cas nuclease technology><Cell Culture Techniques><Clinical Treatment Moab><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Collaborations><Communication><Congo Virus><Congo hemorrhagic fever virus><Cricetinae><Crimean Hemorrhagic Fever Virus><Crimean-Congo Hemorrhagic Fever Virus><Crimean-Congo hemorrhagic fever orthonairovirus><Data><Development><Disease><Disease Outbreaks><Disorder><Dose><Engineering><Ensure><Epidemic Hemorrhagic Fever Virus><Evaluation><Family><Foundations><Four Corners Virus><Four Corners hantavirus><Generations><Glycoproteins><Goals><Golden Hamsters><Golden Syrian Hamsters><Hamsters><Hamsters Mammals><Hantaan virus><Hantavirus><Hemorrhagic Nephroso-Nephritis Virus><Host Factor><Host Factor Protein><Immunization><Immunize><Immunotherapeutic agent><In Vitro><In vivo analysis><Infection><Integration Host Factors><Iowa><Korean Hemorrhagic Fever Virus><Lead><Measurement><Mesocricetus auratus><Mice><Mice Mammals><Modeling><Monoclonal Antibodies><Muerto Canyon Virus><Murine><Mus><Nairovirus><Nipah><Nipah Virus><Nipah henipavirus><Non-Polyadenylated RNA><Outbreaks><Paramyxoviridae><Paramyxovirus><Pathogenesis><Pb element><Play><Position><Positioning Attribute><Preclinical Testing><Predisposition><Proteins><R-Series Research Projects><R01 Mechanism><R01 Program><RNA><RNA Gene Products><RNA Viruses><RNA vaccine><RNA-based vaccine><Recombinants><Research Grants><Research Project Grants><Research Projects><Ribonucleic Acid><Rodent><Rodent Model><Rodentia><Rodents Mammals><Role><Sampling><Services><Sin Nombre hantavirus><Sin Nombre virus><Stress Tests><Surface><Susceptibility><Syrian Hamsters><Testing><Therapeutic><Therapeutic antibodies><Time><Transgenic Animals><Universities><Update><Utah><Vaccines><Validation><Viral><Viral Gene Products><Viral Gene Proteins><Viral Pathogenesis><Viral Proteins><Virus><Virus Replication><adaptive immunity><animal model development><candidate selection><cell culture><cell cultures><developmental><diagnostic tool><disease model><disorder model><efficacy study><efficacy testing><genome editing><genomic editing><heavy metal Pb><heavy metal lead><immune drugs><immune-based therapeutics><immunogen><immunogenicity><immunologic therapeutics><immunotherapeutics><immunotherapy agent><in vitro testing><in vivo><in vivo evaluation><in vivo testing><lead candidate><mAbs><mRNA vaccine><mRNA-based vaccine><medical countermeasure><member><model of animal><monoclonal Abs><nanobodies><nanobody><new vaccines><next generation vaccines><non-human primate><nonhuman primate><novel><novel vaccines><pathogen><phase 1 trial><phase I trial><pre-clinical><pre-clinical testing><preclinical><protective efficacy><prototype><rapid testing><sdAb><single domain antibodies><social role><tool><vaccine antibodies><vaccine candidate><vaccine induced antibodies><vaccine strategy><vaccine-induced antibodies><validations><vascular><viral multiplication><viral replication><virus development><virus host interaction><virus multiplication><virus pathogenesis><virus protein>