Clinical and experimental immunologyJun 1, 2021

Human CD4+ T cells targeting key parts of SARS-CoV-2 Spike and Nucleocapsid proteins with potential for therapy

Updated Dec 28, 2025

Abstract

Nine key immune targets from COVID-19 patients' T cells may aid in developing targeted therapies.

T cell therapy could enhance the effectiveness of current COVID-19 treatments.
Immunocompromised individuals, like recent cancer patients, may benefit from improved immune responses.
The response against two important SARS-CoV-2 proteins, Spike and Nucleocapsid, was assessed.
Clones of virus-reactive CD4T cells were created to identify specific immune responses.
Advanced T cell receptor (TCR) sequencing revealed important TCR-αβ sequences for these clones.
Further studies are needed to confirm these findings for broader applications.

Simplified

Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout 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 neutralizing 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 CD4T cells, we were able to confirm a set of nine and characterize 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, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ 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 CD4T cell therapy of COVID-19. + +

Key numbers

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Strong T cell Response Rate

Proportion of COVID-19 patients showing strong responses to viral antigens.

Identified

Total number of from Spike and Nucleocapsid proteins.

Cytokine Profile Variation

Number of CD4+ T cell clones assessed for cytokine responses.

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Abstract

Key numbers

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