Identification of human CD4+ T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential
Oncology Research and Treatment
; 44(SUPPL 2):288, 2021.
Article
in English
| EMBASE | ID: covidwho-1623610
ABSTRACT
Introduction:
Since December 2019, COVID-19 has spread rapidly across the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as patients after allogeneic haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both shortlived neutralising antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible.Methods:
Activation of CD4+ T cells from 18 COVID-19 patients was determined by flow cytometry, both ex vivo and after in vitro restimulation with SARS-CoV-2 Spike and Nucleocapsid antigens. Immunodominant, 15-mer peptides were identified using epitope mapping. T cells clones specific for these epitopes were further chararacterised for the sensitivity and polarisation of their cytokine responses after in vitro restimulation, by ELISA and cytometric assay. Next-generation sequencing revealed fulllength, paired T Cell Receptor (TCR) αβ sequences.Results:
We identified three patients with strong CD4+ T cells to SARSCoV- 2 antigens. From these patients, 81 T cell clones specific for a selection of 9 immunodominant epitopes (7 Spike and 2 Nucleocapsid epitopes) were generated. Cytokine analysis showed that the sensitivity and polarisation of T cell responses varied depending on the specific epitope. Moreover, TCRαβ sequences revealed an epitope-dependent difference in the level of clonality.Conclusions:
We provide detailed information on SARS-CoV-2-specific CD4+ T cells, including their antigen-specificity, the nature of their cytokine responses and the full sequence of their TCRαβ. These cells have the potential to direct an effective immune response in COVID-19 patients. Our results form a crucial first step towards T cell therapy. Efforts are underway to develop transgenic CD4+ T cells that express the SARS-CoV- 2-specific TCRs identified.
cytokine; endogenous, compound; epitope; nucleocapsid, protein; T, lymphocyte, receptor; T, lymphocyte, receptor, alpha, chain; adult; antigen, specificity; CD4+, T, lymphocyte; cell, clone; cell, therapy; clonal, variation; conference, abstract; controlled, study; cytokine, response; enzyme, linked, immunosorbent, assay; epitope, mapping; ex, vivo, study; flow, cytometry; gene, expression; high, throughput, sequencing; human; human, cell; human, tissue; nonhuman; polarization; protein, expression; Severe, acute, respiratory, syndrome, coronavirus, 2; spike; transgene; virus, nucleocapsid
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Oncology Research and Treatment
Year:
2021
Document Type:
Article
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