Document text
Principal Investigator: JEFFREY M. JACOBSON
Organization: CASE WESTERN RESERVE UNIVERSITY
Fiscal Year: 2022
Award: $483,000
Funding agency: National Institute of Dental and Craniofacial Research
Background. Vaccines against SARS-CoV-2 (CoV-2) do not prevent infection and subsequent
transmission. Strong evidence now implicates the oral cavity as a primary site of acute CoV-2
infection It is therefore incumbent upon us to search for evidence as to why primary mucosal
sites, such as the tongue, remain vulnerable to CoV-2 infection despite vaccination.
Our goal. Immune responses are both innate, which are not specific to an invading pathogen,
and adaptive, which are specific antibody responses. We hypothesize that interrogating oral
epithelial cells and saliva collected from CoV-2 acutely infected unvaccinated and
breakthrough-infected subjects will reveal early and specific innate and adaptive immune
responses that vary with viral load, viral variants, viral clearance, and patient sex and age.
We will collect samples at two time points from acutely infected unvaccinated participants; one
within 7 days and the second within 14 days of testing positive. We will evaluate the relationship
among measures of oral mucosal viral replication, innate and adaptive factors from salivary,
cytological, and serological sources and determine their associations with quantitative viral
measures in the oral mucosa. Innate factors to be analyzed in the saliva include, but not limited
to, cytokines, antimicrobial peptides, interferons (IFN) and secretory IgA that are correlated with
early infection events. To cross validate our results we will also characterize viral strains and
develop novel PCR-based assays for intracellular CoV-2 RNA. Studies will include single cell
RNA sequencing to analyze virus-induced gene expression changes in infected and bystander
cells from the tongue. Full genome sequencing will be used to determine if viral variants are
present and correlate oral immune profiles with variants. Finally we will develop digital PCR
assays to selectively amplify sub genomic CoV-2 RNA as a rapid measure of infected cells. Once
this baseline information is established, we will compare the adaptive and innate oral immune
factors of CoV-2 vaccinated and breakthrough study participants, respectively, to the oral immune
responses in natural infection.
How will we advance the field? This study will allow us to chronicle for the first time the impact
of vaccination on oral immune responses of healthy individuals and compare them to immune
responses from COVID-19-exposed individuals. We anticipate that our integrated accounting of
the oral immune responses during the natural history of SARS-CoV-2 infections will provide an
invaluable reference data set for patients, healthcare professionals and those measuring the
efficacy of antiviral treatments, immunotherapies and vaccines.
Terms: <19S Gamma Globulin><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><7S Gamma Globulin><Accounting><Acute><Address><Aerosols><Affect><Affinity><Age><Antibody Response><Assay><Binding><Bioassay><Biologic Assays><Biological Assay><Biology><Blood><Blood Reticuloendothelial System><Blood Serum><Breathlessness><Brush Cell><Buccal Cavity><Buccal Cavity Head and Neck><Buccal Mucosa><CLIA accredited><CLIA approved><CLIA certified><CLIA compliant><CLIA licensed><COVID-19><COVID-19 exposure><COVID-19 immune response><COVID-19 infection><COVID-19 positive><COVID-19 positivity><COVID-19 vaccination><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID19><COVID19 immune response><COVID19 infection><COVID19 positive><COVID19 positivity><COVID19 vaccination><COVID19 vaccine><COVID19 virus><CV-19><CV19><Cavitas Oris><Cell Body><Cells><Clinical><Clinical Trials><CoV-2><CoV2><Communicable Diseases><Coughing><Cytology><DNA Molecular Biology><Data><Data Set><Dataset><Dyspnea><ELISA><Enrollment><Enzyme-Linked Immunosorbent Assay><Epithelial Cells><Event><Exocrine IgA><Female><Fever><Future><Gender><Gene Expression><Genomics><Goals><Health Care Professional><Health Care Systems><Health Professional><Healthcare Systems><Healthcare professional><Hospital Admission><Hospitalization><Host Defense><IFN><IgA><IgG><IgM><Immune><Immune Markers><Immune mediated therapy><Immune response><Immunes><Immunoglobulin A><Immunoglobulin G><Immunoglobulin M><Immunologic Factors><Immunologic Markers><Immunological Factors><Immunological response><Immunologically Directed Therapy><Immunology><Immunotherapy><Individual><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammatory Response><Innate Immunity><Interferons><Invaded><Laboratories><Longitudinal Studies><Measures><Memory><Molecular><Molecular Biology><Molecular Interaction><Monitor><Mouth><Mouth Mucosa><Native Immunity><Natural History><Natural Immunity><Non-Polyadenylated RNA><Non-Specific Immunity><Nonspecific Immunity><Oral><Oral Medicine><Oral Mucosa><Oral cavity><Oral mucous membrane structure><Outcome><Participant><Patients><Peripheral><Persons><Prognostic Marker><Pyrexia><RNA><RNA Gene Products><RNA vaccine><RNA-based vaccine><Recovery><Response Elements><Ribonucleic Acid><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 exposure><SARS-CoV-2 immune response><SARS-CoV-2 infection><SARS-CoV-2 infection history><SARS-CoV-2 positive><SARS-CoV-2 positivity><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 exposure><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><SIgA><Saliva><Salivary><Sampling><Secretory IgA><Secretory Immunoglobulin A><Serology><Serum><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 corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 immune response><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 positive><Severe acute respiratory syndrome coronavirus 2 positivity><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Site><Source><Stomatology><Symptoms><Testing><Time><Tongue><Transmission><Vaccinated><Vaccination><Vaccinee><Vaccines><Variant><Variation><Viral><Viral Burden><Viral Diseases><Viral Genome><Viral Load><Viral Load result><Virus><Virus Diseases><Virus Replication><Wuhan coronavirus><adaptive immune response><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after severe acute respiratory distress syndrome CoV-2 infection><ages><anti-microbial peptide><anti-viral efficacy><antimicrobial peptide><antiviral efficacy><base><breakthrough infection><cohort><corona virus disease 2019><corona virus disease 2019 vaccine><coronavirus disease 2019><coronavirus disease 2019 exposure><coronavirus disease 2019 immune response><coronavirus disease 2019 infection><coronavirus disease 2019 positive><coronavirus disease 2019 positivity><coronavirus disease 2019 vaccination><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><cytokine><digital><disease severity><enroll><entire genome><enzyme linked immunoassay><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><febrile><febris><field based data><field learning><field study><field test><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following severe acute respiratory distress syndrome CoV-2 infection><full genome><genome sequencing><hCoV19><history of COVID infection><history of COVID-19 infection><host response><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based biomarkers><immune-based therapies><immune-based treatments><immuno therapy><immunologic substance><immunological biomarkers><immunological markers><immunological substance><immunoresponse><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><innovate><innovation><innovative><insight><long-term study><longitudinal outcome studies><longterm study><mRNA vaccine><mRNA-based vaccine><male><member><mucosal site><multidisciplinary><nCoV2><nasopharyngeal swab><new diagnostics><next generation diagnostics><non vaccinated><not vaccinated><novel><novel diagnostics><oral cavity epithelium><oral epithelia><oral epithelium><oral mucosae><oral mucosal><outcome following vaccination><outcome following vaccine><particle><pathogen><post SARS-CoV-2 infection><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><prognostic biomarker><rapid assay><rapid test><rapid tests><recruit><response><result following vaccination><result following vaccine><saliva sample><salivary sample><scRNA-seq><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><sex><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><study population><success><tongue sampling><transmission process><unvaccinated><vaccinate against COVID-19><vaccinate against COVID19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination against COVID-19><vaccination against COVID19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccination outcome><vaccination result><vaccination study><vaccination trial><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 efficacy><vaccine for novel coronavirus><vaccine outcome><vaccine result><vaccine study><vaccine trial><viral RNA><viral infection><viral multiplication><viral replication><viral transmission><virology><virus RNA><virus genome><virus infection><virus multiplication><virus transmission><virus-induced disease><whole genome>