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Series GSE273994

Query DataSets for GSE273994

Status

Public on Aug 06, 2024

Title

Antigen-specific T helper cells predict intensity and longevity of immune responses to SARS-CoV-2 booster vaccination

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

SARS-CoV-2 spike (S) specific T-cell and antibody (AB) responses after primary BNT162b2 vaccination (Pfizer Inc., New York, NY, USA and BioNTech SE, Mainz, Germany) partially depend on the phenotypic composition of pre-existing T-helper (Th) cell populations (Saggau et al., 2022, Immunity). However, adaptive cellular responses and their impact on sustained immune protection after booster vaccination are incompletely understood. We therefore monitored cellular and humoral immune responses before and up to 6 months after the 3rd BNT162b2 vaccination to identify early determinants of sustained responses. As part of an ongoing registry study (Corona Registry Study number 20–426, approved by the ethics committee of the Ludwig Maximilians University Munich), volunteers were recruited among employees of the University Hospital of Augsburg. All subjects had received primary vaccination with two doses of BNT162b2 and were enrolled before their third dose of BNT162b2 (first booster). Exclusion criteria were active infections, receipt of immunomodulatory therapy, pregnancy, positive nucleocapsid-specific (N) IgG titers, and underlying conditions associated with significant impairment of anti-COVID-19 immunity (e.g., diabetes mellitus, cancer, prior stem cell transplantation, or autoimmune diseases). Lithium heparin-anticoagulated whole blood and serum samples were collected immediately before the third vaccination (T0), as well as 1 (T1), 3 (T3), and 6 months (T6) after booster vaccination. No additional booster doses were given during the study period. Serum samples were tested for nucleocapsid (N), S (COBAS e801 immunoassay analyzer with Elecsys Anti-SARS-CoV-2 and Anti-SARS-CoV-2 S (Hitachi Ltd., Tokyo, Japan and Roche Diagnostics GmbH, Basel, Switzerland), and neutralizing AB responses (Haselmann et al., 2020, Clin Chem Med Lab). Subjects developing N IgG or those with incomplete follow-up were excluded. Whole blood was stimulated with co-stimulatory factors anti-CD28 and anti-49d (1 µg/mL Miltenyi Biotec, Bergisch Gladbach, Germany) only, representing the unstimulated/background sample, or additionally S peptides (0.6 nMol/peptide/mL Prot_S, Miltenyi Biotec, Bergisch Gladbach, Germany), as described previously (Lauruschkat et al., 2021, J Fungi (Basel), Weis et al., 2020, Med Mycol). Samples were subsequently analyzed by flow cytometry (data not relevant for this file/analysis) and 13-plex multiplex cytokine assay (LegendPlex Essential Immune Response Panel, BioLegend, San Diego, USA). Significant associations between readouts were identified by multiple testing-adjusted rank correlation analysis.
We found moderate correlation between S IgG (r=0.47), S-induced IL-2 (r=0.58) and IFN-γ (r=0.43) at T1 and T6. S IgG, S-induced IL-2, and S-induced IFN-γ at T6 were significantly associated with increased IL 2 & IL 4, IP 10 & MCP1, and IFN-γ & IP 10 levels at T1, respectively (data presented at the 7th Joint Microbiology & Infection Conference of the German Society for Hygiene and Microbiology (DGHM) and the Association for General and Applied Microbiology (VAAM), Wuerzburg, Germany). Subsequently, the preserved T1 RNA samples of the top and bottom half responders at T6 (based on S IgG, S-induced IL-2, and IFN-γ measurements) were isolated via RNeasy Plus Mini Kit (Qiagen, Hilden, Germany) and analyzed by nCounter Immune Exhaustion Panel (Nanostring, Seattle, USA) as described below. At the time of GEO submission of this data (August 2024), the associated manuscript is under review by Frontiers in Immunology.

Overall design

Top and bottom half of responders 1 month and 6 months after vaccination have been determined as described above. 12 pairs of unstimulated (reference sample) and Prot_S stimulated samples were analysed by nCounter Sprint Immune Exhaustion Panel (total of 24 samples). Transcriptomic data of background-corrected S-induced transcriptional changes at T1 were subsequently analyzed to determine the impact on short- and long-term vaccine responses, i.e. top / bottom half IgG, IL-2, and IFN-γ responder status (as described above) at T1 and T6.

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