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Principal Investigator: Andrea Marzi
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2020
Award: $94,907
Funding agency: National Institute of Allergy and Infectious Diseases
The lab developed 2 vaccine candidates expressing the SARS-CoV-2 spike protein alone or in combination with the Ebola virus glycoprotein (EBOV GP). Hamster studies revealed that a single dose of either vaccine administered intranasally or intramuscularly (IM) protected the animals from disease after SARS-CoV-2 challenge. When we vaccinated rhesus macaques 10 days prior to SARS-CoV-2 challenge with a single dose of the VSV-SARS2-EBOV vaccine, only animals vaccinated by the IM route showed no signs of COVID-19, whereas the IN vaccinated animals did including lung lesions (Furuyama et al., unpublished data).
Together with Dr. Munsters Virus Ecology Section, we studied the receptor usage of beta-coronaviruses using a VSV-based pseudoparticle system. We found that SARS-CoV-2 uses ACE2 as an entry receptor into cells (Letko et al., Nature Microbiology 2020). Furthermore, we collaborated with Dr. Munster on the establishment of a mouse model for SARS-CoV-2 in order to be able to test antivirals and vaccines (Yinda et al., 2020; PMID 32803199).
In order to expand our understanding of human cytokine responses during COVID-19, we are analyzing human serum samples collected over time from patients from Indiana. In addition, we are determining IgG responses to SARS-CoV-2 in these samples and are looking into the potential of antibody-dependent enhancement of infection in these samples (Shifflett, Furuyama et al., unpublished data).
Lastly, TLR4 and TLR7/8 agonists have shown to be beneficial as a treatment against influenza virus infections. In addition, TLR7/8 have been demonstrated to play a role in SARS-CoV-1 infection and pathogenesis. Therefore, we are testing both agonists as a potential treatment against SARS-CoV-2 infections in rodents. This project is in very early stages.
Terms: <2019 novel coronavirus><2019-nCoV><7S Gamma Globulin><Agonist><Animal Diseases><Animals><Antibody-Dependent Enhancement><Antiviral Agents><Antiviral Drugs><Antivirals><Blood Serum><COVID-19><COVID19><Cell Body><Cells><Containment><Coronaviridae><Coronavirus><Cricetinae><Data><Data Set><Dataset><Development><Dose><EBOV><Ebola virus><Ecology><Environmental Science><Glycoproteins><Hamsters><Hamsters Mammals><Homolog of Drosophila TOLL><Human><IgG><Immune response><Immunobiology><Immunoglobulin G><Immunological response><Immunophysiology><Indiana><Infection><Influenza Virus><Intramuscular><Knowledge><Laboratories><Lesion><Lung><Lung Respiratory System><M mulatta><M. mulatta><Macaca mulatta><Microbiology><Modern Man><Molecular Virology><Nature><Pathogenesis><Patients><Play><Proteins><Receptor Protein><Research><Rhesus Macaque><Rhesus Monkey><Rodent><Rodentia><Rodents Mammals><Role><Route><SARS Virus><SARS corona virus><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Sampling><Serum><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe acute respiratory syndrome coronavirus 2><System><TLR4><TLR4 gene><TLR7><TLR7 gene><Testing><Therapeutic><Time><Toll Homologue><Toll-Like Receptor 7><VSV><Vaccinated><Vaccination><Vaccines><Vesicular Stomatitis Virus><Vesicular stomatitis Indiana virus><Viral Diseases><Virus><Virus Diseases><Wuhan coronavirus><anti-viral agents><anti-viral drugs><anti-virals><base><corona virus><corona virus disease 2019><coronavirus disease 2019><cytokine><developmental><ebolavirus><host response><immunoresponse><influenzavirus><innovate><innovation><innovative><mouse model><murine model><pandemic><pandemic disease><particle><pathogenic virus><pulmonary><receptor><response><severe acute respiratory syndrome-CoV><social role><toll-like receptor 4><vaccine candidate><viral infection><viral pathogen><virus infection><virus-induced disease>