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Human CD4+ T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential
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  • Johan Verhagen,
  • Edith Van der Meijden,
  • Vanessa Lang,
  • Andreas Kremer,
  • Simon Völkl,
  • Andreas Mackensen,
  • Michael Aigner,
  • Anita Kremer
Johan Verhagen
Universitätsklinikum Erlangen
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Edith Van der Meijden
Universitätsklinikum Erlangen
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Vanessa Lang
Universitätsklinikum Erlangen
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Andreas Kremer
Universitätsklinikum Erlangen
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Simon Völkl
Universitätsklinikum Erlangen
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Andreas Mackensen
Universitätsklinikum Erlangen
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Michael Aigner
Universitätsklinikum Erlangen
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Anita Kremer
Universitätsklinikum Erlangen
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Abstract

Since December 2019, Coronavirus disease-19 (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 cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived 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. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4+ T cells, we were able to confirm a set of 9 immunodominant epitopes and characterise T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, by using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4+ T cell therapy of COVID-19.

Peer review status:ACCEPTED

19 Mar 2021Submitted to Clinical & Experimental Immunology
22 Mar 2021Submission Checks Completed
22 Mar 2021Assigned to Editor
23 Mar 2021Reviewer(s) Assigned
21 Apr 2021Review(s) Completed, Editorial Evaluation Pending
21 Apr 2021Editorial Decision: Revise Major
27 Apr 20211st Revision Received
28 Apr 2021Reviewer(s) Assigned
19 May 2021Review(s) Completed, Editorial Evaluation Pending
21 May 2021Editorial Decision: Accept