Evaluation of T cell responses with the QuantiFERON SARS-CoV-2 assay in individuals with 3 doses of BNT162b2 vaccine, SARS-CoV-2 infection, or hybrid immunity

Immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or immunization is still under investigation [1]. SARS-CoV-2 infection induces B cell mediated humoral response and a CD4+ and CD8+ T cell response [2], [3], [4], [5]. In patients with coronavirus disease 2019 (COVID-19), early and functional SARS-CoV-2 specific T cell response is associated with mild disease and accelerated viral clearance, whereas T cell lymphocytopenia is associated with severe clinical outcome [5], [6], [7], [8]. Virus-specific T cell-mediated immunity was detected in SARS-CoV-2 exposed individuals, in the absence of seroconversion [9]. In addition, regarding the older coronavirus, SARS-CoV-1, it has been reported that a memory T cell response was detected up to 11 years after infection [8,10].

In parallel, it has been shown that the efficacy of a vaccine against SARS-CoV-2, is not only based on antibody production but also on a robust B and T cell response [11,12]. Also, synergy between memory B cells and T cells possibly plays a crucial role in protection against reinfection [11].

Various methods can be used to assess T cell-mediated immunity against SARS-CoV-2 [4]. Flow cytometry for intracellular cytokine-based assays (FC-ICS) and interferon-γ (IFN-γ) release assays (IGRA) are the most widespread [13]. QuantiFERON (QFN) SARS-CoV-2 assay is a commercially available IGRA, approved for research use for the assessment of cellular immunity after SARS-CoV-2 immunization. The QFN assay is less complex and time-consuming than other T cell assesment techniques, such as flow cytometry [14]. This method has also been used for the assessment of cellular immunity of other infectious diseases, such as cytomegalovirus (CMV) infection in immunocompromised patients and Tuberculosis [15], [16], [17].

Limited data on the long-term duration of cell-mediated immunity have been reported after the third dose of the BNT162b2 mRNA vaccine [18]. Furthermore, the performance of IGRA in unvaccinated children and adults with SARS-CoV-2 infection is still under investigation, especially with the advent of new SARS-CoV-2 variants. The aim of this study is to investigate cellular immune responses elicited by infection and/or vaccination in adults and children, using a commercially available IGRA.

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