Host genetic resistance to COVID-19

Document text

Principal Investigator: Mary N. Carrington
Organization: DIVISION OF BASIC SCIENCES - NCI
Fiscal Year: 2021
Award: $100,619
Funding agency: National Cancer Institute

We are currently performing genetic analyses of several COVID-19 cohorts. These studies are important for design of vaccines and potentially as biomarkers for therapeutic interventions. We are also participating in the COVID-19 Host Genetics Initiative, a collaboration among the human genetics community worldwide to share, generate and analyze data. More than 190 studies are currently underway. We are also collaborating with DCEG on genetic determinants of COVID-19 outcomes and susceptibility. A challenge for the design of peptide vaccines is the diversity of human MHC gene alleles that each have specific preferences for the peptide sequences they display. We are presently collaborating with investigators from MIT and Harvard to develop methodologies that can predict suitable SARS- CoV-2 peptides with high predicted HLA binding affinity for inclusion in MHC class I or II vaccine formulations across diverse populations. For example, structure-based network analyses have identified regions in the SARS-CoV-2 proteome that are mutationally constrained and bear CD8 T cell epitopes that are also conserved in emerging variants as well as other sarbecoviruses. These epitopes elicit stronger CD8 T cell responses in convalescent individuals over mRNA vaccine recipients and provide a framework for a broad T-cell-based vaccine against coronaviruses. The hope is that these data will provide a useful guide to prioritize peptides for inclusion in a vaccine.

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Affinity><Alleles><Allelomorphs><Antibody Response><Antigenic Determinants><Bears><Binding><Binding Determinants><Biological><Biological Markers><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><COVID-19><COVID-19 virus><COVID19><COVID19 virus><CV-19><CV19><Class I Genes><CoV-2><CoV2><Collaborations><Communities><DCEG><Data><Disease Outcome><Division of Cancer Epidemiology and Genetics><Epitopes><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic Determinism><Genetic analyses><Genetic defect><Genotype><Human><Human Genetics><Immune Response Genes><Immune response><Immunological response><Individual><Investigators><Ir Gene><LYT3><Lytotoxicity><MHC Class I><MHC Class I Genes><Methodology><Modern Man><Molecular><Molecular Interaction><Mutation><Network Analysis><Network-based><Outcome><Pathway Analysis><Peptide Vaccines><Peptides><Population Heterogeneity><Predisposition><Proteome><RNA vaccine><RNA-based vaccine><Research Personnel><Researchers><SARS corona virus 2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><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-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 related corona virus 2><Structure><Susceptibility><T cell response><T-Cell Epitopes><T-Cells><T-Lymphocyte><T-Lymphocyte Epitopes><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><Testing><Therapeutic Intervention><Ursidae><Ursidae Family><Vaccine Design><Vaccines><Variant><Variation><Viral><Wuhan coronavirus><base><bear><bio-markers><biologic marker><biomarker><cohort><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 virus><coronavirus vaccine><cytotoxicity><design><designing><develop a vaccine><development of a vaccine><diverse populations><genetic analysis><genetic association><genetic determinant><genetic resistance><genome mutation><hCoV19><heterogeneous population><host response><immune system response><immunoresponse><intervention therapy><mRNA vaccine><mRNA-based vaccine><nCoV2><peptide aminoacid sequence><peptide sequence><population diversity><preference><protein aminoacid sequence><response><thymus derived lymphocyte><vaccine against coronavirus><vaccine development><vaccine formulation>