Steroid treatment suppresses the CD4 + T-cell response to the third dose of mRNA COVID-19 vaccine in systemic autoimmune rheumatic disease patients

• Published in: Scientific reports Vol. 12; no. 1; p. 21056
• Main Authors: Maliah, Avishai, Parikh, Roma, Tayer-Shifman, Oshrat E, Kimhi, Oded, Gepstein, Raz, Halperin, Tami, Levy, Yair, Levy, Carmit, Pri-Paz Basson, Yael, Kivity, Shaye
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 06.12.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: BNT162 Vaccine; CD4 antigen; CD4-Positive T-Lymphocytes; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines; Humans; Immune response; Immune response (humoral); Immune system; Lymphocytes T; mRNA; mRNA vaccines; Patients; Peptides; Rheumatic diseases; Rheumatic Diseases - drug therapy; RNA, Messenger - genetics; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Steroid hormones; Steroids; Tumor necrosis factor-α; Vaccines; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-25642-z

Prolonged steroid treatment has a suppressive effect on the immune system, however, its effect on the cellular response to mRNA vaccine is unknown. Here we assessed the impact of prolonged steroid treatment on the T-cell and humoral response to the SARS-CoV-2 spike (S) peptide following the third dose of the BNT162b2 vaccine in systemic autoimmune rheumatic disease patients. We found that CD4 T-cell response to the S peptide in patients on high-dose long-term steroid treatment showed significantly less S-peptide specific response, compare to low-dose or untreated patients. Remarkably, these results were not reflected in their humoral response, since almost all patients in the cohort had sufficient antibody levels. Moreover, S-peptide activation failed to induce significant mRNA levels of IFNγ and TNFα in patients receiving high-dose steroids. RNA-sequencing datasets analysis implies that steroid treatments' inhibitory effect of nuclear factor kappa-B signaling may interfere with the activation of S-specific CD4 T-cells. This reveals that high-dose steroid treatment inhibits T-cell response to the mRNA vaccine, despite having sufficient antibody levels. Since T-cell immunity is a crucial factor in the immune response to viruses, our findings highlight the need for enhancing the efficiency of vaccines in immune-suppressive patients, by modulation of the T-cell response.