grant

Transmission of CoV-2 and the Impact of Spike Protein Evolution

Organization WASHINGTON UNIVERSITYLocation SAINT LOUIS, UNITED STATESPosted 1 Jul 2023Deadline 30 Jun 2027
NIHUS FederalResearch GrantFY20252019 novel corona virus2019 novel coronavirus2019-nCoV2019-nCoV S protein2019-nCoV spike glycoprotein2019-nCoV spike protein2019-nCoV vaccine2019-nCoV variant2019-nCoV variant forms2019-nCoV variant strains7S Gamma GlobulinACE2Ad vectorAdenoviral VectorAdenovirus VectorAerosolsAffectAgonistAnimal ModelAnimal Models and Related StudiesAnimalsAntibodiesAntigenic DeterminantsBar CodesBindingBinding DeterminantsCOVID-19 S proteinCOVID-19 infectionCOVID-19 predispositionCOVID-19 spikeCOVID-19 spike glycoproteinCOVID-19 spike proteinCOVID-19 susceptibilityCOVID-19 transmissionCOVID-19 vaccineCOVID-19 variantCOVID-19 variant formsCOVID-19 variant strainsCOVID-19 virusCOVID-19 virus infectionCOVID-19 virus transmissionCOVID-19 vulnerabilityCOVID19 infectionCOVID19 virusCessation of lifeChimpChimpanzeeClinical Treatment MoabCoV-2CoV2Coronavirus disease 2019 predispositionCoronavirus disease 2019 susceptibilityCoronavirus disease 2019 vulnerabilityCricetinaeDNA mutationDataDeathDoseEpitopesEventEvolutionFutureGene ModifiedGenetic ChangeGenetic defectGenetic mutationGoalsGolden HamstersGolden Syrian HamstersHamstersHamsters MammalsHourHumanIFNIgAIgGImmuneImmune responseImmunesImmunityImmunizationImmunizeImmunoglobulin AImmunoglobulin GIncubatedIndividualInfectionInfluenza VirusInnate Immune ResponseInnate Immune SystemInnate ImmunityInterferonsIntramuscularKineticsLocationLower respiratory tract structureMeasuresMesocricetus auratusModelingModern ManMolecular InteractionMonoclonal AntibodiesMucosaMucosal ImmunityMucosal TissueMucous MembraneMutationNative ImmunityNatural ImmunityNon-Specific ImmunityNonspecific ImmunityPersonsPhysical distancingPredisposed to COVID-19Predisposed to SARS-CoV-2Predisposed to Severe acute respiratory syndrome coronavirus 2ProcessProteinsPublishingRecombinant InterferonRecombinantsRoleSARS corona virus 2SARS-CO-V2SARS-COVID-2SARS-CoV-2SARS-CoV-2 SSARS-CoV-2 S proteinSARS-CoV-2 infectionSARS-CoV-2 predispositionSARS-CoV-2 spikeSARS-CoV-2 spike glycoproteinSARS-CoV-2 spike proteinSARS-CoV-2 susceptibilitySARS-CoV-2 transmissionSARS-CoV-2 vaccineSARS-CoV-2 variantSARS-CoV-2 variant formsSARS-CoV-2 variant strainsSARS-CoV-2 vulnerabilitySARS-CoV2SARS-CoV2 infectionSARS-associated corona virus 2SARS-associated coronavirus 2SARS-coronavirus-2SARS-coronavirus-2 vaccineSARS-related corona virus 2SARS-related coronavirus 2SARSCoV2Severe Acute Respiratory Coronavirus 2Severe Acute Respiratory Distress Syndrome CoV 2Severe Acute Respiratory Distress Syndrome Corona Virus 2Severe Acute Respiratory Distress Syndrome Coronavirus 2Severe Acute Respiratory Syndrome CoV 2Severe Acute Respiratory Syndrome CoV 2 vaccineSevere Acute Respiratory Syndrome-associated coronavirus 2Severe Acute Respiratory Syndrome-related coronavirus 2Severe acute respiratory syndrome associated corona virus 2Severe acute respiratory syndrome coronavirus 2Severe acute respiratory syndrome coronavirus 2 S proteinSevere acute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 predispositionSevere acute respiratory syndrome coronavirus 2 spike glycoproteinSevere acute respiratory syndrome coronavirus 2 spike proteinSevere acute respiratory syndrome coronavirus 2 susceptibilitySevere acute respiratory syndrome coronavirus 2 vaccineSevere acute respiratory syndrome coronavirus 2 vulnerabilitySevere acute respiratory syndrome related corona virus 2Severity of illnessSocial DistanceSocietiesSyrian HamstersTestingTimeTransmissionUpper Respiratory InfectionsUpper Respiratory Tract InfectionUpper respiratory tractVaccinatedVaccinesVariantVariationViralViral DiseasesVirionVirusVirus DiseasesVirus ParticleWuhan coronavirusadaptive immune responseadaptive immunityadeno vectoradenovectorangiotensin converting enzyme 2angiotensin converting enzyme IIbarcodecoronavirus disease 2019 S proteincoronavirus disease 2019 infectioncoronavirus disease 2019 spike glycoproteincoronavirus disease 2019 spike proteincoronavirus disease 2019 transmissioncoronavirus disease 2019 vaccinecoronavirus disease 2019 variantcoronavirus disease 2019 variant formscoronavirus disease 2019 variant strainscoronavirus disease 2019 viruscoronavirus disease 2019 virus transmissioncoronavirus disease-19 vaccinecoronavirus disease-19 virusdeliver vaccinesdisease severityemerging pathogengene modificationgenetically modifiedgenome mutationhCoV19host responseimmune system responseimmunoresponsein vivoinfected with COVID-19infected with COVID19infected with SARS-CoV-2infected with SARS-CoV2infected with coronavirus disease 2019infected with severe acute respiratory syndrome coronavirus 2infection rateinfluenzavirusinsightlower respiratory tractmAbsmodel of animalmonoclonal AbsnCoV vaccinenCoV-19 vaccinenCoV19 vaccinenCoV2neutralizing mAbneutralizing monoclonal antibodiesnew pathogennovel pathogenparticlepathogenic viruspredisposed to Coronavirus disease 2019preventpreventingprotective effectrate of infectionreceptor bindingreceptor boundrespiratoryrespiratory virusresponsesevere acute respiratory syndrome coronavirus 2 transmissionsevere acute respiratory syndrome coronavirus 2 variantsevere acute respiratory syndrome coronavirus 2 variant formssevere acute respiratory syndrome coronavirus 2 variant strainssocial rolespike proteins on SARS-CoV-2susceptible to COVID-19susceptible to Coronavirus disease 2019susceptible to SARS-CoV-2susceptible to Severe acute respiratory syndrome coronavirus 2transmission processtransmitted COVID-19transmitted SARS-CoV-2transmitted coronavirus disease 2019transmitted severe acute respiratory syndrome coronavirus 2upper airway tractvaccine against 2019-nCovvaccine against COVID-19vaccine against SARS-CoV-2vaccine against SARS-coronavirus-2vaccine against Severe Acute Respiratory Syndrome CoV 2vaccine against Severe acute respiratory syndrome coronavirus 2vaccine candidates against SARS-CoV-2vaccine deliveryvaccine for novel coronavirusvaccines preventing COVIDvaccines to prevent COVIDvariants of concernviral infectionviral pathogenviral transmissionvirus infectionvirus pathogenvirus transmissionvirus-induced diseasevulnerable to COVID-19vulnerable to Coronavirus disease 2019vulnerable to SARS-CoV-2vulnerable to Severe acute respiratory syndrome coronavirus 2
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Full Description

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.

Grant Number: 5R01AI169022-03
NIH Institute/Center: NIH
Principal Investigator: Adrianus Boon

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