Transfer of COVID-19 Immunity Between

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SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The United Patients with serious underlying medical conditions, including immunocompromised cancer patients undergoing hematopoietic cell transplantation, are at higher risk of severe illness from COVID-19. Along with investigations coronavirus epidemic is progressively increasing in the States and other countries with the number of global cases and deaths still climbing. into the virology of SARS-CoV-2, understanding the fundamental immunity of COVID-19 is vital for the rational design of effective therapies. Cellular therapy represents a novel immunotherapeutic modality to treat patients with severe COVID-19 infections. SARS-CoV-2 specific T cells have been detected in most COVID-19 patients; however, there is lack of detailed analysis of the effectiveness and longevity of the virus specific T cells in protecting patients from subsequent SARS-CoV-2 infection. Moreover, immunogenic T cell epitopes have not yet been described, especially for CD4+ T cells critical for linking the cellular and humoral immune responses. The overall goal of this project is to isolate, characterize, and expand SARS-CoV-2 specific T cells to therapeutic doses to provide effective immunotherapy for patients with severe COVID-19 infections. We hypothesize that adoptive transfer of SARS-CoV-2 specific T cells will a) elicitCD4+ and CD8+cellular immunity in patients with current COVID-19 infections; b) persist following adoptive transfer; c) be available for immediate use as off-the-shelf products in an HLA-dependent manner. In our Specific Aims, we propose to extensively investigate the cellular immunity of SARS-CoV-2 specific T cells isolated from patients with previous COVID-19 infections by measuring levels of virus-specific T cells in blood of people with previous COVID-19 infections, characterizing the memory and exhaustion T cell phenotype, and evaluating function against viral antigen in vitro and in vivo. Our team's experience with adoptive immunotherapeutic approaches using virus specific T cells against cytomegalovirus (CMV) and other viruses combined with our established platform for the isolation and expansion of CMV specific T cells, will allow for the rapid large-scale generation of SARS-CoV-2 specific T cells with an array of HLA types and provide an off-the-shelf T cell product for immediate use. Further, by using the novel MHC-PepSeq technology, we will identify immunogenic epitopes restricted by MHC II molecules, which will assist candidate vaccine design and facilitate evaluation of vaccine candidate immunogenicity. Our proposed studies will provide scientific insights into SARS-CoV-2 cellular immunity, which may have broad implications for patients with COVID-19. Moreover, our proposed manufacturing platform will allow us to develop off-the-shelf SARS-CoV-2 specific T cells with different HLA types, which will have a major clinical impact on treatment of patients with severe illness from COVID-19.