Evaluation of the QuantiFERON SARS-CoV-2 interferon-ɣ release assay in mRNA-1273 vaccinated health care workers

Abstract

Current studies focus on cellular and humoral immunity induced by novel SARS-CoV-2 vaccines. Non-responders to vaccinations are not uncommonly encountered in clinical medicine (e.g. in the field of hepatitis B). Whereas vaccine-induced humoral immunity against SARS-CoV-2 is compromised by emerging Variants of Concern (VOCs), cellular immunity against SARS-CoV-2 is emerging as resilient against VOCs. Thus commercially available test kits for diagnostic laboratories designed to evaluate cellular immune responses to SARS-CoV-2 are urgently needed. Here we evaluated the novel QuantiFERON SARS-CoV-2 assay (Qiagen) measuring INF-ɣ release induced by two spike-derived peptide pools (Ag1 and Ag2) in a cohort of health care workers vaccinated with the mRNA-1273 vaccine and confirmed humoral response. Our study indicates the usefulness of this novel assay for routine laboratories to evaluate cellular immunity against SARS-CoV-2 in response to mRNA-1273 vaccination.

Immune response to 2-dose BNT162b2 vaccination and risk of SARS-CoV-2 breakthrough infection: The Shieldvacc-2 study

“…This notion is supported by previous data from pre-SARS-CoV-2 vaccine era that showed a considerable degree of correlation between anti-N and anti-S IgG antibodies generated post-infection. 24 Our finding of poor correlations between antibodies and T-cell responses is consistent with some other studies showing no or low correlations between humoral and cellular immune parameters in vaccinated 25–30 and convalescent 31–33 individuals.…”

The Comparability of Anti-Spike SARS-CoV-2 Antibody Tests is Time-Dependent: a Prospective Observational Study

“…The T cell activity was estimated in prebooster and postbooster whole blood samples using the Quantiferon SARS-CoV-2 assay (Qiagen, Hilden, Germany [ 53 – 55 ]). In brief, we quantified the IFN-γ-release after a 21 h incubation of 1 mL heparinized whole blood portions with two different SARS-CoV-2 antigen mixtures (Ag1, Ag2), and with a negative (“Ce point, IFN-γ) values of the negative (Nil) control were subtracted from the SARS-CoV-2 specific antigen mixes results of the samples and presented as Ag1-Nil and Ag2-Nil, respectively.…”

Novel T cell interferon gamma release assay (IGRA) using spike recombinant protein for COVID19 vaccine response and Nucleocapsid for SARS-Cov2 response

“…Therefore, the provider has established the cut-off in the QuantiFERON assay at 0.350 IU IFN-γ/mL for mycobacterium tuberculosis, at 0.200 IU IFN-γ/mL for cytomegalovirus, and proposed 0.150 IU IFN-γ/mL for SARS-Cov2. When using the QuantiFERON SARS-Cov2 assay in vaccinated healthy individuals following the second injection, the prevalence ranged from 44% when using mRNA-1273 to 80% with BNT162b2 [ 8 , 14 ], which supports the need to optimize the IGRA assay. This can be done, as performed in our study, by taking into consideration several parameters: (i) the use of recombinant proteins instead of overlapping peptides, making it possible to avoid presentation to T cells by antigen presenting cells (APC) of overlapping and degradation peptides; (ii) a large population of non-vaccinated individuals; and (iii) the detection of a specific T cell response distinct from Spike, such as directed against the nucleocapsid, to distinguish vaccination from recent infections and or pre-existing immunity to seasonal human beta-coronaviridae [ 11 ].…”

“…However, this gap can be overcome by using whole blood assays based on the evidence that the blood based interferon-gamma (IFN-γ) release assay (IGRA) is an attractive alternative to ELISpot, as demonstrated for tuberculosis [ 1 ]. Unfortunately, primary whole blood IGRA-based assays using exhaustive libraries of synthetic peptides for Spike and developed for routine use showed limited sensitivity in a COVID19 vaccinated volunteer population [ 8 , 14 ], which limits their clinical application.…”