Scientists have worked at an unprecedented rate to develop vaccines to protect people from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of the coronavirus pandemic (COVID-19). Several vaccines against COVID-19 have received an Emergency Authorization (EUA) from global regulators, and vaccination programs have since begun in most countries around the world.

study: SARS-CoV-2 vaccination diversifies CD4 + reactive T-cell repertoire in patients with previous SARS-CoV-2 infection. Image credit: Design_Cells / Shutterstock


Previous studies have found that COVID-19 vaccines developed by Pfizer-BioNTech and Moderna cause a strong CD4+ T cell responses. The researchers said that unlike natural infection, which requires exogenous or endogenous treatment of several viral proteins, mRNA vaccines lead to the transcription and translation of SARS-CoV-2 peak (S) glycoproteinwhich offers stable immune protection against various antigenic epitopes derived from thorns.

The researchers said there was very limited evidence of immune responses in convalescent individuals of COVID-19 who received the SARS-CoV-2 vaccine. Serum antibody titers are usually assessed to test the duration of immunity to SARS-CoV-2 and CD4.+ helper T cell responses (immune memory cells). These cells determine the concentration of cytotoxic T cells and antibody levels upon re-infection with SARS-CoV-2.

Previous studies have revealed a cross-reaction to CD4+ T cells between SARS-CoV-2 and an endemic common cold coronaviruses (CCC). The immunological memory of cross-reactive T cells must play an important role during current as well as possible future epidemics of zoonotic coronaviruses. Importantly, one study reported that endogenous T-cell responses induced by COVID-19 infection protected macaques from re-infection. However, it is not yet clear whether vaccination of convalescent patients with COVID-19 (CCP) provides additional protection against re-infection or whether natural infection provides adequate protection.

Although a previous study showed that mRNA vaccination increased COVID-19 antibody titers in CCPs more than natural infection, the T-cell response to vaccination in this group is unclear. It is therefore important to determine the clonal nature of the vaccine-induced T-cell repertoire and to evaluate post-vaccination changes in the SARS-CoV-2-reactive T-cell repertoire in CCP.

New study

A new study published in eBioMedicine focuses on determining clonality and levels of SARS-CoV-2-reactive CD4+ T cells in CCPs after vaccination. Researchers also compared this level with vaccinated CCP.

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In this study, researchers performed the Viral Functional Expansion Assay of Specific T Cells (ViraFEST) to determine the reactivity of SARS-CoV-2 at the clonal level of CD4 TCR Vβ. This T cell assay can positively identify antigen-specific T cell receptor (TCR) clonotypes. The ViraFEST analysis helped to evaluate the SARS-CoV-2-specific repertoire produced by vaccination and natural infection. One of the advantages of this assay over conventional ELISPOT or intracellular cytokine stimulation assays is that it can determine reactivity and repertoire at the clonal level. This helped the researchers investigate whether the immune response after vaccination against COVID-19 triggered a cross-reaction or monoreactive T-cell clones of SARS-CoV-2.

Key findings

The researchers said that TCR repertoire diversity, exactly CD4+ T cells are fundamentally multifunctional, thus providing more effective immune protection. In this study, researchers found that vaccination against COVID-19 induced monospecific SARS-CoV-2 reactive T cells with greater functionality.

Several studies have linked high avidity TCR to greater elimination of the virus. These studies emphasize that vaccination is essential for the creation of a long-lasting and dynamic repertoire of SARS-CoV-2-reactive T cells, even in CCPs. The finding of the present study is in line with the above studies. In addition, the present study showed that over time, all patients after vaccination showed significant clonal contraction in both groups, ie. vaccine-induced and infection-induced clones. This finding supports previous reports of declining T-cell responses over time.

More research is needed in the future to assess the duration of vaccine-induced immunity, especially after hybrid and booster vaccination. Not much evidence explains why vaccination against COVID-19 creates a different repertoire of TCR than natural infection. However, the researchers suggest that the mRNA vaccine produces spike-specific T cells that are effective against a wide range of spike epitopes that are highly functional in the presence of IL-2 and IFN-γ. They are usually present due to Th1 memory responses in previously infected cells.

Researchers in this study believe that improved mRNA vaccine formulation and a mono-antigenic approach would help activate a unique repertoire of T cells that is different from those activated during natural infection. In addition, optimized spike transcription and activation of innate sensory molecules can result in different spike epitopes presented on MHC class II molecules. The authors state that there is a possibility that the mono-antigen may reduce the effect of epitope competition from nucleocapsid and non-structural epitopes and thus trigger a different repertoire induced by the vaccine.


One of the limitations of this study is its small group of studies. However, the authors found that the results of this study improved the understanding of the immune repertoire elicited by the COVID-19 vaccine in individuals with a history of SARS-CoV-2 infection. This study highlighted the importance of vaccination in convalescent individuals with COVID-19 to improve the diversity of T-cell responses to SARS-CoV-2 virus.

The story first appeared in News Medical

Clonality and magnitude of SARS-CoV-2-reactive CD4+ T cells in COVID-19 convalescent patients after vaccination

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