SARS-CoV-2 specific memory T lymphocytes from COVID-19 convalescent donors: identification, biobanking and large-scale production for Adoptive Cell Therapy

Abstract

SARS-CoV-2 is causing a second outbreak so the hope for its complete eradication is far from happening. In the absence of effective vaccines, it is mandatory to find effective treatments with low adverse effects able to treat hospitalized patients with COVID-19 disease. In this work, we determined the existence of SARS-CoV-2 specific T cells within the CD45RA- T memory cells from the blood of convalescent donors. Memory T cells can respond quickly to the infection and provide long-term immune protection to reduce the severity of the COVID-19 symptoms. Also, CD45RA- memory T cells confer protection from other pathogens the donors encountered in their life. This is vital to clear other secondary infections usually developed in hospitalized COVID-19 patients. SARS-CoV-2 specific memory T cells were found within all the CD45RA- subsets CD3+, CD4+, CD8+, and in the central memory and effector memory subpopulations. The procedure to obtain the cells is feasible, easy to implement for small scale manufacture, quick and cost-effective involving minimal manipulation, and without GMP condition requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available off-the-shelf to treat moderate/severe cases of COVID-19 increasing the therapeutic options available for these patients.

COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses

“…However, Abs alone appear to be insufficient for viral clearance. Adoptive transfer of SARS-CoV-2-enriched T cells from COVID-19 convalescent donors might be a therapeutic option for patients with severe disease ( Ferreras et al., 2020 ; Leung et al., 2020 ), but is restricted by the availability of HLA-matched donors with sufficient SARS-CoV-2-specific T cell frequencies. The risk of graft-versus-host disease (GvHD) due to alloreactivity and the risk of induction of cytokine storm syndrome and lung damage are major concerns ( Mehta et al., 2020 ; Ong et al., 2020 ).…”

“…Ferreras et al. postulated that in vitro depletion of Tn cells via CD45RA would result in immediately available, ‘off-the-shelf’ SARS-CoV-2-specific memory T cell products ( Ferreras et al., 2020 ).…”

“…The risk of graft-versus-host disease (GvHD) due to alloreactivity and the risk of induction of cytokine storm syndrome and lung damage are major concerns (Mehta et al, 2020;Ong et al, 2020). Ferreras et al postulated that in vitro depletion of Tn cells via CD45RA would result in immediately available, 'off-the-shelf' SARS-CoV-2-specific memory T cell products (Ferreras et al, 2020).…”

SARS-CoV-2 variant B.1.1.7 caused HLA-A2+CD8+T cell epitope mutations for impaired cellular immune response

“…However, a couple of studies have shown that antibody titres decline fast in some convalescent patients, indicating a short duration of humoral immunity (Sette and Crotty, 2021). On the other hand, current studies have demonstrated that specific T cell responses emerge in most of the COVID-19 patients during the early stage of the infection (Ferreras et al, 2021).…”

“…However, a couple of studies have shown that antibody titres decline fast in some convalescent patients, indicating a short duration of humoral immunity(Sette and Crotty, 2021). On the other hand, current studies have demonstrated that specific T cell responses emerge in most of the COVID-19 patients during the early stage of the infection(Ferreras et al, 2021). Although significant reduction in T cell counts was observed in severe COVID-19 patients, the revealed antigen specific T cell response indicated their important role in resolving SARS-CoV-2 infection(Grifoni et al, 2020; Le Bert et al, 2020; Weiskopf et al, 2020).…”