Vaccinated and Convalescent Donor-Derived Severe Acute Respiratory Syndrome Coronavirus 2-Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients.
COVID-19
T-cell responses
adoptive immunotherapy
coronavirus 2
virus-specific T cells
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
received:
05
03
2021
pubmed:
28
4
2021
medline:
15
12
2021
entrez:
27
4
2021
Statut:
ppublish
Résumé
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). 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33905481
pii: 6255711
doi: 10.1093/cid/ciab371
pmc: PMC8135332
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2073-2082Subventions
Organisme : NIH HHS
Pays : United States
Organisme : Institute of Applied Biosciences
Organisme : Centre for Research and Technology Hellas
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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