T cell responses to SARS-CoV-2 vaccination in people with multiple sclerosis differ between disease-modifying therapies

Abstract

Immune responses in people with multiple sclerosis (pwMS) on 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 antibody responses after vaccination. Evaluation of cellular responses after vaccination is therefore of particular importance in these populations. In this study, we analysed CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy controls and pwMS on five different DMTs by flow cytometry. Although pwMS on anti-CD20 and S1PR therapies had low antibody responses after both 2 and 3 vaccine doses, T cell responses in pwMS on anti-CD20 therapies were preserved after third vaccination, even when additional anti-CD20 treatment was administered between vaccine doses 2 and 3. PwMS taking S1PR modulators 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 antibody responses vaccination can generate immune responses in pwMS.

The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination

“…Whilst the majority on SARS-CoV-2 vaccine responses have focused on antibody responses, reduced T-cell recall responses have also repeatedly been reported during fingolimod treatment in many small studies that are perhaps consistent with the induced T cell lymphopenia ( Wu et al, 2022 , Gombolay et al, 2022 , Tallantyre et al, 2022a , Meyer-Arndt et al, 2022 , Wolf et al, 2022 *). The peripheral blood T cell responses in people treated with the more recent S1PR modulators have been inconsistent and further study is required ( Rauser et al, 2022 *), ( Kantor, 2022 *), ( Akgün et al, 2022 *).…”