SARS-CoV-2–specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein
| Autor: | Ashley Geiger, Hua Liang, Jessica Durkee-Shock, Catherine M. Bollard, Allistair Abraham, C. Russell Cruz, Eva M. Stevenson, Patrick J. Hanley, Fahmida Hoq, R. Brad Jones, Maja Stanojevic, Christopher A. Lazarski, Anushree Datar, Kajal Chaudhry, Zoe Shancer, Haili Lang, Jeffrey I. Cohen, Emily K. Reynolds, Mariah Jensen-Wachspress, Madeline Terpilowski, Ping-Hsien Lee, Kathleen Webber, Robert Ulrey, Kathleen Ferrer, Vaishnavi V. Kankate, Krista Gangler, Katherine M. Harris, Nan Zhang, Stéphanie Val, Peter D. Burbelo, Uduak Ekanem, Michael D. Keller, Lesia K. Dropulic |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Immunobiology and Immunotherapy medicine.medical_treatment T-Lymphocytes Immunology Cell Culture Techniques Epitopes T-Lymphocyte Inflammation Biochemistry Immunotherapy Adoptive Epitope Viral Proteins Young Adult Interferon Immunity medicine Humans Pandemics Aged business.industry Immunodominant Epitopes SARS-CoV-2 COVID-19 Membrane Proteins Cell Biology Hematology Immunotherapy Middle Aged Virology In vitro COVID-19 Drug Treatment Vaccination Membrane protein Female medicine.symptom business medicine.drug |
| Zdroj: | Blood |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described in recovered patients, and may be important for immunity following infection and vaccination as well as for the development of an adoptive immunotherapy for the treatment of immunocompromised individuals. In this report, we demonstrate that SARS-CoV-2–specific T cells can be expanded from convalescent donors and recognize immunodominant viral epitopes in conserved regions of membrane, spike, and nucleocapsid. Following in vitro expansion using a good manufacturing practice-compliant methodology (designed to allow the rapid translation of this novel SARS-CoV-2 T-cell therapy to the clinic), membrane, spike, and nucleocapsid peptides elicited interferon-γ production, in 27 (59%), 12 (26%), and 10 (22%) convalescent donors (respectively), as well as in 2 of 15 unexposed controls. We identified multiple polyfunctional CD4-restricted T-cell epitopes within a highly conserved region of membrane protein, which induced polyfunctional T-cell responses, which may be critical for the development of effective vaccine and T-cell therapies. Hence, our study shows that SARS-CoV-2 directed T-cell immunotherapy targeting structural proteins, most importantly membrane protein, should be feasible for the prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients with blood disorders or after bone marrow transplantation to achieve antiviral control while mitigating uncontrolled inflammation. Key Points • Coronavirus-specific polyfunctional T cells can be expanded from convalescent individuals for use for patients after bone marrow transplant. • SARS-CoV-2 T-cell products target structural viral proteins, including commonly recognized regions in the C terminus of membrane protein. |
| Databáze: | OpenAIRE |
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