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T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis
Asia-Sophia Wolf, Anthony Ravussin, Marton König, Mathias H. Øverås, Guri Solum, Ingrid Fadum Kjønstad, Adity Chopra, Trygve Holmøy, Hanne F. Harbo, Silje Watterdal Syversen, Kristin Kaasen Jørgensen, Einar August Høgestøl, Jon Torgils Vaage, Elisabeth G. Celius, Fridtjof Lund-Johansen, Ludvig A. Munthe, Gro Owren Nygaard, Siri Mjaaland
Asia-Sophia Wolf, Anthony Ravussin, Marton König, Mathias H. Øverås, Guri Solum, Ingrid Fadum Kjønstad, Adity Chopra, Trygve Holmøy, Hanne F. Harbo, Silje Watterdal Syversen, Kristin Kaasen Jørgensen, Einar August Høgestøl, Jon Torgils Vaage, Elisabeth G. Celius, Fridtjof Lund-Johansen, Ludvig A. Munthe, Gro Owren Nygaard, Siri Mjaaland
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Research Article COVID-19 Immunology

T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis

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Abstract

Immune responses in people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have been of significant interest throughout the COVID-19 pandemic. Lymphocyte-targeting immunotherapies, including anti-CD20 treatments and sphingosine-1-phosphate receptor (S1PR) modulators, attenuate Ab responses after vaccination. Evaluation of cellular responses after vaccination, therefore, is of particular importance in these populations. In this study, we used flow cytometry to analyze CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy control study participants and pwMS receiving 5 different DMTs. Although pwMS receiving rituximab and fingolimod therapies had low Ab responses after both 2 and 3 vaccine doses, T cell responses in pwMS taking rituximab were preserved after a third vaccination, even when an additional dose of rituximab was administered between vaccine doses 2 and 3. PwMS taking fingolimod had low detectable T cell responses in peripheral blood. CD4 and CD8 T cell responses to SARS-CoV-2 variants of concern Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. Our results indicate the importance of assessing both cellular and humoral responses after vaccination and suggest that, even in the absence of robust Ab responses, vaccination can generate immune responses in pwMS.

Authors

Asia-Sophia Wolf, Anthony Ravussin, Marton König, Mathias H. Øverås, Guri Solum, Ingrid Fadum Kjønstad, Adity Chopra, Trygve Holmøy, Hanne F. Harbo, Silje Watterdal Syversen, Kristin Kaasen Jørgensen, Einar August Høgestøl, Jon Torgils Vaage, Elisabeth G. Celius, Fridtjof Lund-Johansen, Ludvig A. Munthe, Gro Owren Nygaard, Siri Mjaaland

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Figure 4

T cell responses to the Delta and Omicron SARS-CoV-2 variants after 3 vaccine doses.

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T cell responses to the Delta and Omicron SARS-CoV-2 variants after 3 va...
(A) Schematic of mutated regions in the Alpha, Delta, and Omicron regions stimulated by peptides. The SARS-CoV-2 spike protein is 1273 aa long and consists of the signal peptide and S1 and S2 subunits; the RBD in S1 is indicated in red (59). Regions covered by the SARS-CoV-2 Prot_S (WT) peptide used for activation-induced marker assays are shown for reference. The control and mutant peptides for each variant cover the same loci but with the mutated (mutant) or Wuhan-Hu-1 variant (control). The aa mutations are listed in Methods. PBMCs from rituximab-treated patients after a third vaccine dose were stimulated with spike peptide pools from the mutated regions (blue circles) of the Alpha (n = 29), Delta (n = 41), and Omicron (n = 21) VOC and the same regions of the WT sequence (empty circles), and the CD4+ (B) and CD8+ (C) T cell responses were compared. Statistical differences were calculated by Wilcoxon signed-rank tests with the Holm-Šídák method for multiple comparisons. *P < 0.05, **P < 0.01.

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