Document text
Principal Investigator: Adrianus CM Boon
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2023
Award: $581,630
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
SARS-CoV-2 has led to unprecedented disruptions to society, killing more than 6 million people worldwide. It is
a respiratory virus whose main mode of transmission is via respiratory droplets and aerosols. Social distancing
and vaccines have greatly decreased the rate of infection and transmission. Despite these efforts, SARS-CoV-
2 transmission has continued. Moreover, different variants of concern, harboring signature mutations in the virus
attachment Spike protein, have emerged. How these changes affect transmission of SARS-CoV-2 in naïve,
infected and immunized individuals is not known. The transmission bottleneck is defined as the number of unique
virus particles that establish an infection in the recipient host. This number is important as it determines the rate
of evolution of the virus and the immune threshold required for protection from infection. This application will use
barcoded or tagged SARS-CoV-2 to quantify how many virus particles establish an infection in the recipient host.
We will use the Syrian hamster SARS-CoV-2 airborne transmission model to define how the innate and adaptive
immune response in the donor and recipient host effect the number of unique transmission events. Using
genetically modified hamsters that are deficient in their type I or III interferon response will be used to measure
the role of innate immunity on SARS-CoV-2 transmission to the upper respiratory tract (URT) and subsequent
dissemination of the virus to lower respiratory tract (LRT). Transmission and dissemination of SARS-CoV-2 will
also be quantified in recipient animals that were previously infected with SARS-CoV-2, immunized with mucosal
and systemic COVID-19 vaccines, or received neutralizing IgG and IgA antibodies. Finally, this application will
measure the impact of immune escape on the transmission bottleneck in immune recipients. Fundamental
insights into respiratory virus transmission and dissemination, transmission bottleneck and defining correlates of
protection in the URT and LRT will inform future vaccine efforts against respiratory viruses.
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Alteration><Genetic Change><Genetic defect><Goals><Golden Hamsters><Golden Syrian Hamsters><Hamsters><Hamsters Mammals><Hour><Human><IFN><IgA><IgG><Immune><Immune response><Immunes><Immunity><Immunization><Immunize><Immunoglobulin A><Immunoglobulin G><Immunological response><Incubated><Individual><Infection><Influenza Virus><Innate Immune Response><Innate Immune System><Innate Immunity><Interferons><Intramuscular><Kinetics><Location><Lower respiratory tract structure><Measures><Mesocricetus auratus><Modeling><Modern Man><Molecular Interaction><Monoclonal Antibodies><Mucosa><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Mutation><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Pan Genus><Pan Species><Persons><Physical distancing><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Process><Proteins><Publishing><Recombinant Interferon><Recombinants><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 predisposition><SARS-CoV-2 susceptibility><SARS-CoV-2 transmission><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV-2 vulnerability><SARS-CoV2><SARS-CoV2 infection><SARS-CoV2 vaccine><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 predisposition><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome coronavirus 2 vulnerability><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Social Distance><Societies><Syrian Hamsters><Testing><Time><Transmission><Upper Respiratory Infections><Upper Respiratory Tract Infection><Upper respiratory tract><Vaccinated><Vaccines><Variant><Variation><Viral><Viral Diseases><Virion><Virus><Virus Diseases><Virus Particle><Wuhan coronavirus><adaptive immune response><adaptive immunity><adeno vector><adenovector><angiotensin converting enzyme 2><angiotensin converting enzyme II><barcode><corona virus disease 2019 vaccine><coronavirus disease 2019 infection><coronavirus disease 2019 transmission><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease 2019 virus transmission><coronavirus disease-19 vaccine><coronavirus disease-19 virus><deliver vaccines><disease severity><emerging pathogen><genome mutation><hCoV19><host response><immune system response><immunoresponse><in vivo><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><infection rate><influenzavirus><insight><lower respiratory tract><mAbs><model of animal><monoclonal Abs><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neutralizing mAb><neutralizing monoclonal antibodies><new pathogen><novel pathogen><particle><pathogenic virus><predisposed to Coronavirus disease 2019><prevent><preventing><protective effect><rate of infection><receptor binding><receptor bound><respiratory><respiratory virus><response><severe acute respiratory syndrome coronavirus 2 transmission><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><social role><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><transmission process><transmitted COVID-19><transmitted SARS-CoV-2><transmitted coronavirus disease 2019><transmitted severe acute respiratory syndrome coronavirus 2><upper airway tract><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine delivery><vaccine for novel coronavirus><variants of concern><viral infection><viral pathogen><viral transmission><virus infection><virus pathogen><virus transmission><virus-induced disease>