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Principal Investigator: Mark Morris Davis
Organization: STANFORD UNIVERSITY
Fiscal Year: 2024
Award: $377,760
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT – Project 2
The goal of Project 2 is to assess T cell responses in the context of proposed studies of: (i) COVID-19
vaccines that utilize novel platforms (mRNA) or adjuvants (Matrix M used in the Novavax vaccine) and (ii)
Humans given broad spectrum antibiotics that disrupt their microbiome, prior to and during rabies vaccination.
This goal is highly synergistic with those of Projects 1 and 3, which will evaluate innate and B cell responses
respectively, in the context of the same clinical trials. We will use new developed state-of-the-art techniques
that will allow us to probe the vaccine responses here with an unprecedented scale and depth. The three
methods are: (1) spheromer probes for specific T cells, (2) GLIPH (for Grouping of Lymphocyte Interactions by
Paratope Hotspots) analysis of TCR specificity groups, and (3) immune organoids. We will apply these tools in
the following aims:
Aim 1: Assessment of T cell responses to vaccination against COVID-19.
Sub-aim 1a. Analyze T cell responses induced by the BNT162b2 mRNA vaccine in healthy versus atopic
individuals. We will use the spheromer technology mentioned above, to create and use a panel of pMHC
Spheromers SARS-CoV-2 spike epitopes covering the major class I and II HLA alleles, to analyze the T cell
response, in healthy versus atopic subjects. In addition, we will perform TCR repertoire analysis using GLIPH2
to analyze both bulk and single cell TCR sequences in order to define the frequency, phenotype, function and
TCR diversity of antigen specific T cell responses to primary and secondary vaccination in blood and the
draining lymph nodes of both healthy adults and allergy prone subjects.
Sub-aim 1b: Assessment of T cell responses induced by the Novavax Matrix-M adjuvanted subunit vaccine.
We will also analyze samples collected from a Novavax sponsored trial done at the University of Witwatersrand
with spheromers and TCR sequence analysis and determine how the response to an adjuvanted subunit
vaccine differs from that induced by mRNA vaccination
Aim 2: Assessment of the impact of the microbiota on the antigen-specific T cell response to
vaccination. We will assess the impact of broad-spectrum antibiotics on the primary T cell response to rabies
vaccination. In particular, we will analyze the TCR repertoire and phenotype of T cells responding to this
vaccine, since there are clear indications that the microbiome can influence T cell phenotype, and we
hypothesize that there might be an influence on the repertoire as well.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV vaccine><21+ years old><Adjuvant><Adult><Adult Human><Algorithms><Alleles><Allelomorphs><Allergic Reaction><Allergy><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Antibody Binding Sites><Antigenic Determinants><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><BNT 162b2><BNT162b2><Binding Determinants><Blood><Blood Reticuloendothelial System><CDR3-region><COVID-19><COVID-19 S protein><COVID-19 spike><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 vaccination><COVID-19 vaccine><COVID-19 virus><COVID19 virus><CV-19><Cell Body><Cells><Clinical Trials><CoV-2><CoV2><Complementarity Determining Region 3><Complementarity Determining Region III><Coronavirus Infectious Disease 2019><Defect><Epitopes><Exposure to><Ferritin><Frequencies><GI microbiota><Gastrointestinal microbiota><Goals><Grouping><Human><Hypersensitivity><Immune><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Individual><Influenza Vaccines><Innate Immunity><Label><Lymphatic cell><Lymphocyte><Lymphocytic><Messenger RNA><Methods><Miscellaneous Antibiotic><Modern Man><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Organoids><Paratopes><Peptide-MHC><Peptide-Major Histocompatibility Protein Complex><Peptide/MHC Complex><Peptides><Pfizer covid19 vaccine><Pfizer-BioNTech COVID-19 vaccine><Pfizer-BioNTech coronavirus disease 2019 vaccine><Pfizer/BioNTech vaccine><Phenotype><Probability><RNA immunization><RNA vaccination><RNA vaccine><RNA-based vaccine><Rabies Human Diploid Cell Vaccine><Rabies Vaccines><Reporting><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S><SARS-CoV-2 S protein><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-CoV2><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><SEQ-AN><Sampling><Sequence Analyses><Sequence Analysis><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 S protein><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Specificity><Spinal Column><Spine><Staining method><Stains><Subunit Vaccines><Survey Instrument><Surveys><T cell response><T-Cells><T-Lymphocyte><T-cell receptor repertoire><TCR repertoire><Techniques><Technology><Universities><Vaccination><Vaccines><Vertebral column><Wuhan coronavirus><adaptive immunity><adult youth><adulthood><antibody combining site><antigen-specific T cells><backbone><biological systems><cohort><combinatorial><complementarity-determining region 3><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 vaccination><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus 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lymphocyte><tool><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine against flu><vaccine against influenza><vaccine candidates against SARS-CoV-2><vaccine for novel coronavirus><vaccine response><vaccine responsiveness><vaccine-induced response><vaccines preventing COVID><vaccines to prevent COVID><young adult><young adulthood>