Abstract
AbstractT-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.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus first reported in December 2019 from Wuhan, China, is responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19).[1]
Recent reports have suggested that immunocompromised patients may be at high risk of severe and potentially prolonged disease, suggesting that T-cell immunity is essential for overcoming COVID19.12,13 Studies of the related virus SARS-CoV demonstrated that T cells recognizing viral epitopes within SARS-CoV structural proteins were integral in viral clearance, and remained detectable for .10 years after exposure.[14,15]
Knowledge of T-cell epitopes recognized in other viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus have successfully led to the development of adoptive immunotherapy with ex vivo expanded virus-specific T cells (VSTs)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus first reported in December 2019 from Wuhan, China, is responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19).[1]. Knowledge of T-cell epitopes recognized in other viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus have successfully led to the development of adoptive immunotherapy with ex vivo expanded virus-specific T cells (VSTs) This approach has been highly successful in preventing or treating viral infections in high-risk patients after bone marrow transplant (BMT) with minimal risk of graft-versus-host disease.[16,17] To date, .1000 patients have been treated internationally in phase 1/2 protocols using VSTs.[18,19,20,21,22,23,24] Importantly, expansion of VSTs in vivo correlates strongly with antiviral efficacy.[23,25,26] the expansion of such approaches to include SARS-CoV-2–specific T cells may offer protection from COVID-19 to these vulnerable individuals. It provides proof of concept for optimal donor section for the rapid manufacture of good manufacturing practice (GMP)-compliant SARS-CoV-2–specific T-cell therapeutics, with the potential to prevent or treat COVID-19 in immunocompromised patients with blood disorders and/or after BMT
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