Rapid, simplified whole blood-based multiparameter assay to quantify and phenotype SARS-CoV-2-specific T-cells

Riou, Catherine; Schäfer, Georgia; Bruyn, Elsa Du; Goliath, René; Stek, Cari; Mou, Huihui; Hung, Deli; Wilkinson, Katalin A.; Wilkinson, Robert J.

doi:10.1183/13993003.00285-2021

Cited by 15 publications

(9 citation statements)

References 44 publications

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“…Peptide Pools for the T-Cell-Based Tests SARS-CoV-2 PepTivator Peptide Pools (Miltenyi Biotec) covering the sequence of SARS-CoV-2 spike protein (Pep-Tivator SARS-CoV-2 Prot_S1, Prot_S, and Prot_S+) were used. [24][25][26] The PepTivator Peptide Pools are constituted by peptides of 15 amino acid length with 11 amino acid overlap.…”

Section: Health Care Workersmentioning

confidence: 99%

Humoral- and T-Cell–Specific Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients With MS Using Different Disease-Modifying Therapies

Tortorella

Aiello²,

Gasperini³

et al. 2022

Neurology

142

192

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Objective:To evaluate the immune-specific response after the full SARS-CoV-2 vaccination of multiple sclerosis (MS) patients treated with different Disease Modifying drugs by the detection of both serological- and T-cell responses.Methods:Health care workers (HCWs) and MS patients, having completed the two-dose schedule of an mRNA-based vaccine against SARS-CoV-2 in the last 2-4 weeks, were enrolled from two parallel prospective studies conducted in Rome, Italy, at the National Institute for Infectious diseases Spallanzani–IRCSS and San Camillo Forlanini Hospital. Serological response was evaluated by quantifying the Region-Binding-Domain (RBD) and neutralizing-antibodies. Cell-mediated response was analyzed by a whole-blood test quantifying interferon (IFN)-γ response to spike peptides. Cells responding to spike stimulation were identified by FACS analysis.Results:We prospectively enrolled 186 vaccinated individuals: 78 HCWs and 108 MS patients. Twenty-eight MS patients were treated with IFN-β, 35 with fingolimod, 20 with cladribine, and 25 with ocrelizumab. A lower anti-RBD-antibody response rate was found in patients treated with ocrelizumab (40%, p<0.0001) and fingolimod (85.7%, p=0.0023) compared to HCWs and patients treated with cladribine or IFN-β. Anti-RBD-antibody median titer was lower in patients treated with ocrelizumab (p<0.0001), fingolimod (p<0.0001) and cladribine (p=0.010) compared to HCWs and IFN-β-treated patients. Importantly, serum neutralizing activity was present in all the HCWs tested and only in a minority of the fingolimod-treated patients (16.6%). T-cell-specific response was detected in the majority of MS patients (62%), albeit with significantly lower IFN-γ levels compared to HCWs. The lowest frequency of T-cell response was found in fingolimod-treated patients (14.3%). T-cell-specific response correlated with lymphocyte count and anti-RBD antibody titer (rho=0.554, p<0.0001 and rho=0.255, p=0.0078 respectively). Finally, IFN-γ T-cell response was mediated by both CD4+ and CD8+ T cells.Conclusion:mRNA vaccines induce both humoral and cell-mediated specific immune responses against spike peptides in all HCWs and in the majority of MS patients. These results carry relevant implications for managing vaccinations suggesting to promote vaccination in all treated MS patients.Classification of Evidence:This study provides Class III data that COVID mRNA vaccination induces both humoral and cell-mediated specific immune responses against viral spike proteins in a majority of MS patients.

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Section: Health Care Workersmentioning

confidence: 99%

Humoral- and T-Cell–Specific Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients With MS Using Different Disease-Modifying Therapies

Tortorella

Aiello²,

Gasperini³

et al. 2022

Neurology

142

192

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“…The assessment of the percentage of CD4 and CD8 T cells was performed on cryopreserved fixed whole blood as described 55 . Briefly bood was collected in sodium heparin tubes and processed within 3 h of collection.…”

Section: T Cell Stimulation By Sars-cov-2 Peptidesmentioning

confidence: 99%

Effects of tuberculosis and/or HIV-1 infection on COVID-19 presentation and immune response in Africa

et al. 2023

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Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8% are HIV-1 co-infected. Two or more co-morbidities are present in 57.7% of participants, including HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p < 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8% participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis.

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“…To evaluate the specific IFN-g-Spike (S)-specific T-cell response, a whole-blood platform was used (20,(23)(24)(25)(26)(27)(28)(29). We stimulated the whole blood with a pool of peptides that covered the SARS-CoV-2-S protein sequence (SARS-CoV-2 PepTivator ® Prot_S1, Prot_S, and Prot_S+, cat.…”

Section: Ifn-g Whole-blood Assaymentioning

confidence: 99%

Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis

et al. 2022

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ObjectiveTo assess the kinetics of the humoral and cell-mediated responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in rheumatoid arthritis (RA) patients treated with different immunosuppressive therapies.MethodsFollowing vaccine completed schedule, health care workers (HCWs, n = 49) and RA patients (n = 35) were enrolled at 5 weeks (T1) and 6 months (T6) after the first dose of BNT162b2-mRNA vaccination. Serological response was assessed by quantifying anti-receptor-binding domain (RBD)-specific immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibodies, while cell-mediated response was assessed by a whole-blood test quantifying the interferon (IFN)-γ response to spike peptides. B-cell phenotype and IFN-γ-specific T-cell responses were evaluated by flow cytometry.ResultsAfter 6 months, anti-RBD antibodies were still detectable in 91.4% of RA patients, although we observed a significant reduction of the titer in patients under Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)-Ig [median: 16.4 binding antibody units (BAU)/ml, interquartile range (IQR): 11.3–44.3, p < 0.0001] or tumor necrosis factor (TNF)-α inhibitors (median: 26.5 BAU/ml, IQR: 14.9–108.8, p = 0.0034) compared to controls (median: 152.7 BAU/ml, IQR: 89.3–260.3). All peripheral memory B-cell (MBC) subpopulations, in particular, the switched IgG+ MBCs (CD19+CD27+IgD-IgM-IgG+), were significantly reduced in RA subjects under CTLA-4-Ig compared to those in HCWs (p = 0.0012). In RA patients, a significantly reduced anti-RBD IgG titer was observed at T6 vs. T1, mainly in those treated with CTLA-4-Ig (p = 0.002), interleukin (IL)-6 inhibitors (p = 0.015), and disease-modifying antirheumatic drugs (DMARDs) ± corticosteroids (CCSs) (p = 0.015). In contrast, a weak nonsignificant reduction of the T-cell response was reported at T6 vs. T1. T-cell response was found in 65.7% of the RA patients at T6, with lower significant magnitude in patients under CTLA-4-Ig compared to HCWs (p < 0.0001). The SARS-CoV-2 IFN-γ-S-specific T-cell response was mainly detected in the CD4+ T-cell compartment.ConclusionsIn this study, in RA patients after 6 months from COVID-19 vaccination, we show the kinetics, waning, and impairment of the humoral and, to a less extent, of the T-cell response. Similarly, a reduction of the specific response was also observed in the controls. Therefore, based on these results, a booster dose of the vaccine is crucial to increase the specific immune response regardless of the immunosuppressive therapy.

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Rapid, simplified whole blood-based multiparameter assay to quantify and phenotype SARS-CoV-2-specific T-cells

Cited by 15 publications

References 44 publications

Humoral- and T-Cell–Specific Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients With MS Using Different Disease-Modifying Therapies

Humoral- and T-Cell–Specific Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients With MS Using Different Disease-Modifying Therapies

Effects of tuberculosis and/or HIV-1 infection on COVID-19 presentation and immune response in Africa

Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis

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