In-depth analysis of SARS-CoV-2–specific T cells reveals diverse differentiation hierarchies in vaccinated individuals

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines pose as the most effective approach for mitigating COVID-19 pandemic. High-degree efficacy of SARS-CoV-2 vaccines in clinical trials indicate that vaccination invariably induces an adaptive immune response. However, the emergence of breakthrough infections in vaccinated individuals suggest that the breadth and magnitude vaccine-induced adaptive immune response may varies. We assessed vaccine-induced SARS-CoV-2 Tcell response in twenty-one vaccinated individuals and found that SARS-CoV-2 specific T-cells, which mainly CD4+ T-cell, were invariably detected in all individuals but the response was varied. We then investigated differentiation states and cytokine profiles to identify immune features associated with superior recall function and longevity. We identified SARS-CoV-2 specific CD4+ T-cells were polyfunctional and produced high levels of IL-2, which could be associated with superior longevity. Based on the breadth and magnitude of vaccine-induced SARS-CoV-2 response, we identified two distinct response groups: individuals with high abundance vs low abundance of SARS-CoV-2 Tcells. The fractions of TNF-a and IL-2 producing SARS-CoV-2 T-cells were the main determinants distinguishing high vs low responders. Lastly, we identified the majority of vaccine-induced SARS-CoV-2 T-cells were reactive against non-mutated regions of mutant S-protein, suggesting that vaccine-induced SARS-CoV-2 T-cells could provide continued protection against emerging variants-of-concern.

SARS-CoV-2 Specific Antibody Response and T Cell-Immunity in Immunocompromised Patients up to Six Months Post COVID: A Pilot Study

“…In addition, the lack of difference in T cells specific for spike peptides between vaccinated and unvaccinated patients may reflect limitations of the vaccines to induce T cell responses. The detection of SARS-CoV-2-specific CD8 T cells was restricted to two immunocompromised patients with high CD8 T cell counts and two immunocompetent patients that had been vaccinated, which is in line with previous findings illustrating that COVID-19 vaccination elicits CD4 T cell dominant immune responses [ 33 ]. Memory T cells rapidly express effector activity after antigen recognition presented by non-professional antigen presenting cells.…”

Immune correlates of protection by vaccine against SARS‐CoV‐2 in patients with chronic lymphocytic leukaemia

“…This cellular response was independent of the serological status as T‐cell responses were elicited in the absence or presence of circulating antibodies, consistent with a non‐redundant role as key determinants of immune protection against COVID‐19 26 . This contribution of a T‐cellular response to vaccination might implement the compromised humoral immunity protection against various current and emerging SARS‐CoV‐2 variants 49 …”

“…26 This contribution of a T-cellular response to vaccination might implement the compromised humoral immunity protection against various current and emerging SARS-CoV-2 variants. 49 This study showed that CLL-directed treatments influenced the magnitude of spike-specific T-cell responses to vaccine. Analysis on CLL treatment subgroups revealed a significantly higher production of IFNγ and TNFα by CD4 + T cells in patients under a BTK inhibitor compared to other treatments, while cytokine levels in CD8 + T cells were not influenced by CLL treatment.…”

“… 26 This contribution of a T‐cellular response to vaccination might implement the compromised humoral immunity protection against various current and emerging SARS‐CoV‐2 variants. 49 …”

High‐resolution analysis of individual spike peptide‐specific CD4+ T‐cell responses in vaccine recipients and COVID‐19 patients

“…[81][82][83] The assessment of cytokine production in response to the peptide pool would allow assumptions with regard to the T-cell (poly-) functionality. 28,84,85 Most importantly, the assessment of cellular immunity towards SARS-CoV-2 using these peptides in combination with the antibody status could provide a better understanding of the adaptive immune response and facilitate more refined public health interventions. 86 Other groups could show that the T-cell and antibody responses against SARS-CoV-2 spike glycoprotein remain effective against the currently dominating B.1.1.529 VoC.…”