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

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.

Automated summary

This study investigates the immune responses of people with multiple sclerosis receiving disease-modifying therapies (DMTs) to COVID-19 vaccination. The study finds that lymphocyte-targeting immunotherapies attenuate antibody responses, and thus, evaluating cellular responses after vaccination is crucial. The results show that although pwMS receiving rituximab and fingolimod therapies had low antibody responses, T cell responses in pwMS taking rituximab were preserved after a third vaccination. PwMS taking fingolimod had low detectable T cell responses in peripheral blood, and T cell responses to SARS-CoV-2 variants Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. These findings highlight the importance of assessing both cellular and humoral responses after vaccination in pwMS and suggest that vaccination can generate immune responses even in the absence of robust antibody responses.