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Principal Investigator: Carrie Mae Long
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2020
Award: $880,868
Funding agency: National Institute of Allergy and Infectious Diseases
Coxiella burnetii is a bacterium that can cause a severe flu-like illness in humans known as Q fever. This zoonotic infection is typically acquired via aerosol transmission of contaminated byproducts of infected ruminants. The pronounced infectivity and environmental stability of C. burnetii highlights its utility as a potential bioweapon. The public health impact of Q fever was illustrated by a recent dairy goat-associated outbreak in the Netherlands resulting in nearly 4000 human cases. This outbreak demonstrated the human health burden and staggering economic losses that can result from this infectious disease. Despite Coxiella burnetii's endemicity and potential for harm, both as a zoonosis and a potential bioweapon, much still remains unknown regarding host-pathogen interactions. Additionally, a safe and effective vaccine licensed for use in the United States remains elusive due to a potential post-vaccination hypersensitivity response. We are particularly interested in understanding virulence mechanisms, immune correlates of vaccine-mediated immunity, and mechanisms of post-vaccination hypersensitivity. Thus, we have developed guinea pig models of infection, vaccination-challenge, and post-vaccination hypersensitivity. We have utilized these models to identify novel virulence factors of C. burnetii, screen vaccine candidates, and work towards developing a less reactive vaccine. These models, combined with genetic manipulation of the bacteria, have provided novel insight into the pathogenesis of and host response to C. burnetii.
As part of NIAID/RMLs response to the COVID-19 pandemic, Dr. Carrie Long collaborated with Dr. Andrea Marzi's laboratory (LV) to evaluate the efficacy of SARS-CoV-2 therapeutics and vaccines in vivo. Toll-like receptor 4 agonists were tested as potential SARS-CoV-2 therapeutics in Syrian golden hamsters while VSV- based vaccines were evaluated in the same model system. Assistance was provided with study preparation, animal infection, animal monitoring, and necropsy.
Terms: <2019 novel coronavirus><2019-nCoV><Aerosols><Agonist><Allergy><Animal Model><Animal Models and Related Studies><Animals><Autopsy><Bacteria><Biologic Models><Biological Models><C burnetii><C. burnetii><COVID-19 epidemic><COVID-19 pandemic><COVID19 epidemic><COVID19 pandemic><Caprine Species><Cavia><Cell Body><Cells><Collaborations><Communicable Diseases><Coxiella burnetii><DNA Alteration><DNA Sequence Alteration><DNA mutation><Development><Disease><Disease Outbreaks><Disease Outcome><Disorder><Economics><Exhibits><Future><Genes><Genetic><Genetic mutation><Genome><Genomics><Goat><Goats Mammals><Golden Hamsters><Golden Syrian Hamsters><Guinea Pigs><Guinea Pigs Mammals><Health><Homolog of Drosophila TOLL><Host Factor><Host Factor Protein><Human><Hypersensitivity><Hypersensitivity skin testing><Immune><Immune response><Immunes><Immunity><Immunobiology><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunophysiology><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Integration Host Factors><Laboratories><Length><Lesion><Lipopolysaccharides><Mediating><Mesocricetus auratus><Model System><Modeling><Modern Man><Monitor><Mouse Strains><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Netherlands><Organism><Outbreaks><Pathogenesis><Pathogenicity Factors><Phase><Preparation><Proteins><Public Health><Q Fever><Reagent><Regulation><Research><Role><Ruminantia><Ruminants><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Sequence Alteration><Severe acute respiratory syndrome coronavirus 2><Site><Skin Tests><Syrian Hamsters><T4SS><TLR4><TLR4 gene><Testing><Therapeutic><Toll Homologue><Transmission><Tropism><Type IV Secretion System><Type IV Secretion System Pathway><United States><United States National Institutes of Health><VSV><Vaccination><Vaccines><Vesicular Stomatitis Virus><Vesicular stomatitis Indiana virus><Virulence><Virulence Factors><Work><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><base><biological weapon><bioweapon><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019 epidemic><coronavirus disease 2019 pandemic><design><designing><developmental><dosage><entire genome><flu><full genome><gene manipulation><genetic manipulation><genetically manipulate><genetically perturb><genome sequencing><genomic alteration><host response><human disease><hypersensitivity test><immunologic skin test><immunoresponse><improved><in vivo><in vivo Model><insight><interest><living system><model of animal><model organism><mouse model><murine model><mutant><necropsy><novel><pathogen><postmortem><response><social role><toll-like receptor 4><transmission process><type 4 secretion system><vaccine candidate><vaccine evaluation><vaccine screening><vaccine testing><whole genome>