Accuracy of QuantiFERON SARS-CoV-2 research use only assay and characterization of the CD4+ and CD8+ T cell-SARS-CoV-2 response: comparison with a homemade interferon-γ release assay

Aiello, Alessandra; Coppola, Andrea; Vanini, Valentina; Petrone, Linda; Cuzzi, Gilda; Salmi, Andrea; Altera, Anna Maria Gerarda; Tortorella, Carla; Gualano, Gina; Gasperini, Claudio; Scolieri, Palma; Beccacece, Alessia; Vita, Serena; Bruzzese, Vincenzo; Lorenzetti, Roberto; Palmieri, Fabrizio; Nicastri, Emanuele; Goletti, Delia

doi:10.1016/j.ijid.2022.07.049

Cited by 26 publications

(29 citation statements)

References 38 publications

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“…To evaluate the proportion of vaccine responders, we set the threshold at 0.15 IU/ml, as previously described [ 19 , 20 ] and considered cases as responders if any of their Ag1 or Ag2 values were higher than that level. The percentage of ocrelizumab responders was 87.5% after two doses ( N = 23) and 100% after three doses ( N = 22).…”

Section: Resultsmentioning

confidence: 99%

A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies

et al. 2023

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Background Most people with Multiple Sclerosis (pwMS) are subjected to immunomodulatory disease-modifying treatments (DMTs). As a result, immune responses to COVID-19 vaccinations could be compromised. There are few data on cellular immune responses to the use of COVID-19 vaccine boosters in pwMS under a broad spectrum of DMTs. Methods In this prospective study, we analysed cellular immune responses to SARS-CoV-2 mRNA booster vaccinations in 159 pwMS with DMT, including: ocrelizumab, rituximab, fingolimod, alemtuzumab, dimethyl fumarate, glatiramer acetate, teriflunomide, natalizumab and cladribine. Results DMTs, and particularly fingolimod, interact with cellular responses to COVID-19 vaccination. One booster dose does not increase cellular immunity any more than two doses, except in the cases of natalizumab and cladribine. SARS-CoV-2 infection combined with two doses of vaccine resulted in a greater cellular immune response, but this was not observed after supplementary booster jabs. Ocrelizumab-treated pwMS who had previously received fingolimod did not develop cellular immunity, even after receiving a booster. The time after MS diagnosis and disability status negatively correlated with cellular immunity in ocrelizumab-treated pwMS in a booster dose cohort. Conclusions After two doses of SARS-CoV-2 vaccination, a high response yield was achieved, except in patients who had received fingolimod. The effects of fingolimod on cellular immunity persisted for more than 2 years after a change to ocrelizumab (which, in contrast, conserved cellular immunity). Our results confirmed the need to find alternative protective measures for fingolimod-treated people and to consider the possible failure to provide protection against SARS-CoV-2 when switching from fingolimod to ocrelizumab.

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Section: Resultsmentioning

confidence: 99%

A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies

et al. 2023

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“…Anti-RBD-IgG were indicated as positive when ≥7.1 BAU/mL. For the T-cell response evaluated by IFN-γ release assay (IGRA), whole blood was overnight stimulated with a peptide mix (0.1 µg/mL of each peptide pool) covering the SARS-CoV-2 spike protein (Miltenyi Biotec, Germany) or with the staphylococcal enterotoxin B (SEB) at 200 ng/mL, as positive control 24 25. Plasma IFN-γ levels were measured using an automatic ELISA (ELLA, protein simple, R&D Systems, Minnesota, USA).…”

Section: Methodsmentioning

confidence: 99%

Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies

Aiello

Coppola

Ruggieri

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundThe decline of humoral response to COVID-19 vaccine led to authorise a booster dose. Here, we characterised the kinetics of B-cell and T-cell immune responses in patients with multiple sclerosis (PwMS) after the booster dose.MethodsWe enrolled 22 PwMS and 40 healthcare workers (HCWs) after 4–6 weeks from the booster dose (T3). Thirty HCWs and 19 PwMS were also recruited 6 months (T2) after the first dose. Antibody response was measured by anti-receptor-binding domain (RBD)-IgG detection, cell-mediated response by an interferon (IFN)-γ release assay (IGRA), Th1 cytokines and T-cell memory profile by flow cytometry.ResultsBooster dose increased anti-RBD-IgG titers in fingolimod-treated, cladribine-treated and IFN-β-treated patients, but not in ocrelizumab-treated patients, although antibody titres were lower than HCWs. A higher number of fingolimod-treated patients seroconverted at T3. Differently, T-cell response evaluated by IGRA remained stable in PwMS independently of therapy. Spike-specific Th1-cytokine response was mainly CD4+T-cell-mediated, and in PwMS was significantly reduced (p<0.0001) with impaired IL-2 production compared with HCWs at T3. In PwMS, total Th1 and IFN-γ CD4+T-cell responders to spike protein were increased from T2 to T3.Compared with HCWs, PwMS presented a higher frequency of CD4+and CD8+terminally differentiated effector memory cells and of CD4+effector memory (TEM) cells, independently of the stimulus suggesting the association of this phenotype with MS status. CD4+and CD8+TEMcell frequency was further increased at T3 compared with T2.ConclusionsCOVID-19 vaccine booster strengthens humoral and Th1-cell responses and increases TEMcells in PwMS.

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“…In a 48-well flat-bottom plate whole-blood was stimulated or not with the described Pool S (spike) at 0.1 μg/mL and SEB (Sigma- Aldrich, St. Loius, MO, USA) at 200 ng/mL (positive control) and then treated or not with recombinant human IL-10. The plate was incubated overnight (20–24 h) at 37°C, 5% CO 2 , and then plasma was collected and stored at − 80°C until use ( 24 , 28 ).…”

Section: Methodsmentioning

confidence: 99%

“…In a 48-well flat-bottom plate whole-blood was stimulated or not with the described Pool S (spike) at 0.1 mg/mL and SEB The plate was incubated overnight (20-24 h) at 37°C, 5% CO 2 , and then plasma was collected and stored at − 80°C until use (24,28).…”

Section: Whole-blood Assaymentioning

confidence: 99%

Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy

et al. 2022

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ObjectiveSeveral therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, through the ex-vivo assessment of the effects of exogenous IL-10 on SARS-CoV-2-specific-response using a whole-blood platform.MethodsTwo cohorts were evaluated: in “study population A”, plasma levels of 27 immune factors were measured by a multiplex (Luminex) assay in 39 hospitalized “COVID-19 patients” and 29 “NO COVID-19 controls” all unvaccinated. In “study population B”, 29 COVID-19 patients and 30 NO COVID-19-Vaccinated Controls (NO COVID-19-VCs) were prospectively enrolled for the IL-10 study. Whole-blood was stimulated overnight with SARS-COV-2 antigens and then treated with IL-10. Plasma was collected and used for ELISA and multiplex assay. In parallel, whole-blood was stimulated and used for flow cytometry analysis.ResultsBaseline levels of several immune factors, including IL-10, were significantly elevated in COVID-19 patients compared with NO COVID-19 subjects in “study population A”. Among them, IL-2, FGF, IFN-γ, and MCP-1 reached their highest levels within the second week of infection and then decreased. To note that, MCP-1 levels remained significantly elevated compared with controls. IL-10, GM-CSF, and IL-6 increased later and showed an increasing trend over time. Moreover, exogenous addition of IL-10 significantly downregulated IFN-γ response and several other immune factors in both COVID-19 patients and NO COVID-19-VCs evaluated by ELISA and a multiplex analysis (Luminex) in “study population B”. Importantly, IL-10 did not affect cell survival, but decreased the frequencies of T-cells producing IFN-γ, TNF-α, and IL-2 (p<0.05) and down-modulated HLA-DR expression on CD8+ and NK cells.ConclusionThis study provides important insights into immune modulating effects of IL-10 in COVID-19 and may provide valuable information regarding the further in vivo investigations.

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Accuracy of QuantiFERON SARS-CoV-2 research use only assay and characterization of the CD4+ and CD8+ T cell-SARS-CoV-2 response: comparison with a homemade interferon-γ release assay

Cited by 26 publications

References 38 publications

A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies

A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies

Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies

Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy

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