Identification of immuno-dominant T cell epitopes for immunotherapy against SARS-CoV-2

The current outbreak of the novel coronavirus SARS-CoV-2 has 375,313 confirmed cases worldwide with 16,361 deaths as of March 23, 2020, and 8,547 cases and 118 deaths in Switzerland. A preventive vaccine is expected to be approved for distribution, but in only 12-18 months, and several immune-modulatory drugs are being tested around the world. While most of the vaccine currently under developments rely on inducing antibody responses from computational predictions, so far, there is limited information about immuno-dominant T cell epitopes in the virus proteome. However, such information is critical as it would allow the development of immunotherapy against SARS-CoV-2, as well as provide a toolset for immuno-monitoring of patients. The aim of this study is to identify dominant epitopes for immuno-targeting of SARS-CoV-2. By applying proteogenomics analytical methods, and by combining transcriptomics and mass spectrometry based immunopeptidomics, we seek to uncover the in vivo presented HLA ligandome using an in vitro system of antigen presenting cells loaded with viral proteins or long peptides, and when possible, using infected cell lines or infected lung tissue surgically removed during warm autopsy procedures from deceased patients. Immune recognition of the identified viral epitopes in recovered or acutely infected patients will be evaluated experimentally with antigen-specific T cell based assays. This discovery effort will provide critical information about immune responses against SARS-CoV-2 and will reveal the dominant epitopes from different viral isolates that are most effective in inducing effective CD8+ and CD4+ T cell responses. Such epitopes could be further developed into immunotherapeutic. Furthermore, we wish to gain new insight about potential variants in the virus genome and about particular HLA allotypes that are associated with, or lead to, impaired presentation of such epitopes and that would be advantageous for viral spreading.