Host genetic resistance to COVID-19

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

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.