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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 3

Readministration of rituximab (RTX) between vaccine doses affects Ab but not T cell responses.

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Readministration of rituximab (RTX) between vaccine doses affects Ab but...
Rituximab-treated individuals were grouped by whether they received a dose of RTX between V2 and V3. (A) Ab titers (BAU/mL) after the V2 and V3 vaccine doses for patients who did not receive RTX between vaccines (empty boxes) (n = 20–32) and patients who did receive RTX between vaccines (gray boxes) (n = 23–30). (B) CD4 T cell and (C) CD8 T cell responses without stimulation (unstim) or to SARS-CoV-2 spike or CMV peptides after third vaccine dose for patients without (n = 28) or with RTX administration (n = 28) between vaccine doses. Statistical analyses for paired responses by Wilcoxon signed-rank tests, unpaired responses by Mann-Whitney tests, and 2-tailed P values are shown, *P < 0.05. All t tests were corrected for multiple comparisons by Benjamini-Hochberg FDR method.

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