Vaccinated and Convalescent Donor–Derived Severe Acute Respiratory Syndrome Coronavirus 2–Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients. (27th April 2021)

• Record Type: Journal Article
• Authors: Papayanni, Penelope-Georgia; Chasiotis, Dimitrios; Koukoulias, Kiriakos; Georgakopoulou, Aphrodite; Iatrou, Anastasia; Gavriilaki, Eleni; Giannaki, Chrysavgi; Bitzani, Militsa; Geka, Eleni; Tasioudis, Polychronis; Chloros, Diamantis; Fylaktou, Asimina; Kioumis, Ioannis; Triantafyllidou, Maria; Dimou-Besikli, Sotiria; Karavalakis, Georgios; Boutou, Afroditi K; Siotou, Eleni; Anagnostopoulos, Achilles; Papadopoulou, Anastasia; Yannaki, Evangelia
• Is Part Of: Clinical infectious diseases. Volume 73:Number 11(2021)
• Page Start: 2073
• Page End: 2082
• Publication Date: 2021-04-27
• Subjects: coronavirus 2 -- COVID-19 -- T-cell responses -- adoptive immunotherapy -- virus-specific T cells; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciab371
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19). Methods: We first tested SARS-CoV-2–specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19–infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)–positive subjects, vaccinated individuals, non–intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment. Results: We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2–specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2–specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity. Conclusions: Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an "off-the shelf" T-cell immunotherapy for high-risk patients. Abstract : Polyclonal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific–specific T-cell products with a safe and strong cytotoxic profile against SARS-CoV-2–presenting targets, as well as SARS-CoV-2 variants, can be generated from both coronavirus disease 2019 convalescent or vaccinated donors to be used as adoptive therapy of high-risk patients.