tetano
Editor, Senior Moderator
Clin Infect Dis
. 2021 Apr 27;ciab371.
doi: 10.1093/cid/ciab371. Online ahead of print.
Vaccinated and convalescent donor-derived SARS-CoV-2-specific T cells as adoptive immunotherapy for high-risk COVID-19 patients
Penelope-Georgia Papayanni[SUP] 1 2 [/SUP], Dimitrios Chasiotis[SUP] 1 2 [/SUP], Kiriakos Koukoulias[SUP] 1 2 [/SUP], Aphrodite Georgakopoulou[SUP] 1 2 [/SUP], Anastasia Iatrou[SUP] 3 [/SUP], Eleni Gavriilaki[SUP] 1 [/SUP], Chrysavgi Giannaki[SUP] 4 [/SUP], Militsa Bitzani[SUP] 4 [/SUP], Eleni Geka[SUP] 5 [/SUP], Polychronis Tasioudis[SUP] 5 [/SUP], Diamantis Chloros[SUP] 6 [/SUP], Asimina Fylaktou[SUP] 7 [/SUP], Ioannis Kioumis[SUP] 8 [/SUP], Maria Triantafyllidou[SUP] 1 [/SUP], Sotiria Dimou-Besikli[SUP] 1 [/SUP], Georgios Karavalakis[SUP] 1 [/SUP], Afroditi K Boutou[SUP] 6 [/SUP], Eleni Siotou[SUP] 1 [/SUP], Achilles Anagnostopoulos[SUP] 1 [/SUP], Anastasia Papadopoulou[SUP] 1 [/SUP], Evangelia Yannaki[SUP] 1 9 [/SUP]
Affiliations
Abstract
Background: 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 (C?V-2-ST) immunity and expansion in unexposed donors, COVID-19 infected individuals (convalescent), asymptomatic PCR-positive subjects, vaccinated individuals, non-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 variant. 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+ 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.
Keywords: COVID-19; T cell responses; adoptive immunotherapy; coronavirus 2; virus-specific T cells.
. 2021 Apr 27;ciab371.
doi: 10.1093/cid/ciab371. Online ahead of print.
Vaccinated and convalescent donor-derived SARS-CoV-2-specific T cells as adoptive immunotherapy for high-risk COVID-19 patients
Penelope-Georgia Papayanni[SUP] 1 2 [/SUP], Dimitrios Chasiotis[SUP] 1 2 [/SUP], Kiriakos Koukoulias[SUP] 1 2 [/SUP], Aphrodite Georgakopoulou[SUP] 1 2 [/SUP], Anastasia Iatrou[SUP] 3 [/SUP], Eleni Gavriilaki[SUP] 1 [/SUP], Chrysavgi Giannaki[SUP] 4 [/SUP], Militsa Bitzani[SUP] 4 [/SUP], Eleni Geka[SUP] 5 [/SUP], Polychronis Tasioudis[SUP] 5 [/SUP], Diamantis Chloros[SUP] 6 [/SUP], Asimina Fylaktou[SUP] 7 [/SUP], Ioannis Kioumis[SUP] 8 [/SUP], Maria Triantafyllidou[SUP] 1 [/SUP], Sotiria Dimou-Besikli[SUP] 1 [/SUP], Georgios Karavalakis[SUP] 1 [/SUP], Afroditi K Boutou[SUP] 6 [/SUP], Eleni Siotou[SUP] 1 [/SUP], Achilles Anagnostopoulos[SUP] 1 [/SUP], Anastasia Papadopoulou[SUP] 1 [/SUP], Evangelia Yannaki[SUP] 1 9 [/SUP]
Affiliations
- PMID: 33905481
- DOI: 10.1093/cid/ciab371
Abstract
Background: 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 (C?V-2-ST) immunity and expansion in unexposed donors, COVID-19 infected individuals (convalescent), asymptomatic PCR-positive subjects, vaccinated individuals, non-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 variant. 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+ 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.
Keywords: COVID-19; T cell responses; adoptive immunotherapy; coronavirus 2; virus-specific T cells.