A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies

Abstract

Background Most people with Multiple Sclerosis (pwMS) are subjected to immunomodulatory disease-modifying treatments (DMTs). As a result, immune responses to COVID-19 vaccinations could be compromised. There are few data on cellular immune responses to the use of COVID-19 vaccine boosters in pwMS under a broad spectrum of DMTs. Methods In this prospective study, we analysed cellular immune responses to SARS-CoV-2 mRNA booster vaccinations in 159 pwMS with DMT, including: ocrelizumab, rituximab, fingolimod, alemtuzumab, dimethyl fumarate, glatiramer acetate, teriflunomide, natalizumab and cladribine. Results DMTs, and particularly fingolimod, interact with cellular responses to COVID-19 vaccination. One booster dose does not increase cellular immunity any more than two doses, except in the cases of natalizumab and cladribine. SARS-CoV-2 infection combined with two doses of vaccine resulted in a greater cellular immune response, but this was not observed after supplementary booster jabs. Ocrelizumab-treated pwMS who had previously received fingolimod did not develop cellular immunity, even after receiving a booster. The time after MS diagnosis and disability status negatively correlated with cellular immunity in ocrelizumab-treated pwMS in a booster dose cohort. Conclusions After two doses of SARS-CoV-2 vaccination, a high response yield was achieved, except in patients who had received fingolimod. The effects of fingolimod on cellular immunity persisted for more than 2 years after a change to ocrelizumab (which, in contrast, conserved cellular immunity). Our results confirmed the need to find alternative protective measures for fingolimod-treated people and to consider the possible failure to provide protection against SARS-CoV-2 when switching from fingolimod to ocrelizumab.

Long-Term Immune Response Profiles to SARS-CoV-2 Vaccination and Infection in People with Multiple Sclerosis on Anti-CD20 Therapy

“…T-cellular antiviral responses appeared to decrease in the months following primary vaccination and to increase upon booster vaccination in both untreated and anti-CD20-treated groups, but pairwise comparisons between the different timepoints did not reach statistical significance. These results correspond to another study that also did not find statistically significant differences in T-cell responses before and after booster vaccination [ 30 ]. Conversely, several other studies had reported a relevant decrease in virus-specific T-cell responses in the months after primary vaccination and a significant increase upon booster vaccination [ 16 , 18 , 28 ].…”

“…Concerning T-cell responses to SARS-CoV-2 vaccination, several studies demonstrated an increase of virus-specific T-cells in ocrelizumab-treated pwMS after the booster vaccination compared to the last measurement before the booster [ 16 , 18 , 28 ]. In contrast, another study reported similar levels of SARS-CoV-2-specific T-cell responses before and after the booster vaccine shot [ 30 ].…”

Targeting Inflammasome Activation in Viral Infection: A Therapeutic Solution?

“…Dimethyl fumarate, the FDA-approved drug for multiple sclerosis, induces succination of GSDMD, blocking the interaction of GSDMD with caspases and subsequent cell death [ 120 ]. Dimethyl fumarate is currently in clinical trials for multiple sclerosis patients infected with SARS-CoV-19 ( Table 1 ) [ 121 , 122 ]. The different function of inflammasomes in myeloid cells and other types of immune cells must be taken into account when developing therapies targeting the inflammasomes.…”

mRNA COVID-19 Vaccination Does Not Exacerbate Symptoms or Trigger Neural Antibody Responses in Multiple Sclerosis

“… 8 The booster also increased the cellular response in patients treated with fingolimod (80%) and reduced the proportion of patients without any response, which is different from previous studies. 6 , 27 No significant differences were seen between patients on ocrelizumab or rituximab. Of note, the humoral responses still remain quantitatively impaired after a fourth dose in patients treated with ocrelizumab.…”