SARS-CoV-2-specific T cells generated for adoptive immunotherapy are capable of recognizing multiple SARS-CoV-2 variants

Adoptive T-cell immunotherapy has provided promising results in the treatment of viral complications in humans, particularly in the context of immunocompromised patients who have exhausted all other clinical options. The capacity to expand T cells from healthy immune individuals is providing a new approach to anti-viral immunotherapy, offering rapid off-the-shelf treatment with tailor-made human leukocyte antigen (HLA)-matched T cells. While most of this research has focused on the treatment of latent viral infections, emerging evidence that SARS-CoV-2-specific T cells play an important role in protection against COVID-19 suggests that the transfer of HLA-matched allogeneic off-the-shelf virus-specific T cells could provide a treatment option for patients with active COVID-19 or at risk of developing COVID-19. We initially screened 60 convalescent individuals and based on HLA typing and T-cell response profile, 12 individuals were selected for the development of a SARS-CoV-2-specific T-cell bank. We demonstrate that these T cells are specific for up to four SARS-CoV-2 antigens presented by a broad range of both HLA class I and class II alleles. These T cells show consistent functional and phenotypic properties, display cytotoxic potential against HLA-matched targets and can recognize HLA-matched cells infected with different SARS-CoV-2 variants. These observations demonstrate a robust approach for the production of SARS-CoV-2-specific T cells and provide the impetus for the development of a T-cell repository for clinical assessment. Author summary Since the emergence of SARS-CoV-2 variants that reduce the effectiveness of vaccines, it is evident that other interventional strategies will be needed to treat COVID-19, particularly in patients with a compromised immune system who are at an increased risk of developing severe COVID-19. Off-the-shelf T-cell immunotherapy is proving to be a powerful tool to treat viral disease in patients with a compromised immune system. Here, we report here that a small number of SARS-CoV-2 exposed individuals can be used generate a bank of specific T cells that provide broad population coverage. Importantly, we demonstrate that most of the epitopes recognized by these T cells remain unchanged in different variants and that the T cells can recognize cells infected with three different variants of SARS-CoV-2. We believe these observations provide critical proof-of-concept that T-cell based immunotherapy may offer an option for the future treatment of immunocompromised patients who remain susceptible to the severe complications associated with COVID-19.

Automated summary

Adoptive T-cell immunotherapy has shown promising results in treating viral complications, especially in immunocompromised patients. Expanding T cells from healthy individuals provides a new approach to antiviral immunotherapy with rapid and customized treatment options. Recent research indicates that SARS-CoV-2-specific T cells play a crucial role in protecting against COVID-19, suggesting the potential of using HLA-matched virus-specific T cells for treating active COVID-19 or at-risk patients.