Differential effects of selective versus unselective sphingosine 1-phosphate receptor modulators on T- and B-cell response to SARS-CoV-2 vaccination

Research output: Contribution to journalResearch articleContributedpeer-review



Background: Sphingosine 1-phosphat receptor modulators (S1PRMs) have been linked to attenuated immune response to SARS-CoV-2 vaccines. Objective: To characterize differences in the immune response to SARS-CoV-2 vaccines in patients on selective versus unselective S1PRMs. Methods: Monocentric, longitudinal study on people with multiple sclerosis (pwMS) on fingolimod (FTY), siponimod (SIP), ozanimod (OZA), or without disease-modifying therapy (DMT) following primary and booster SARS-CoV-2 vaccination. Anti-SARS-CoV-2 antibodies and T-cell response was measured with electro-chemiluminescent immunoassay and interferon-γ release assay. Results: Primary vaccination induced a significant antibody response in pwMS without DMT while S1PRM patients exhibited reduced antibody titers. The lowest antibodies were found in patients on FTY, whereas patients on OZA and SIP presented significantly higher levels. Booster vaccinations induced increased antibody levels in untreated patients and comparable titers in patients on OZA and SIP, but no increase in FTY-treated patients. While untreated pwMS developed a T-cell response, patients on S1PRMs presented a diminished/absent response. Patients undergoing SARS-CoV-2 vaccination before onset of S1PRMs presented a preserved, although attenuated humoral response, while T-cellular response was blunted. Conclusion: Our data confirm differential effects of selective versus unselective S1PRMs on T- and B-cell response to SARS-CoV-2 vaccination and suggest association with S1PRM selectivity rather than lymphocyte redistribution.


Original languageEnglish
Pages (from-to)1849-1859
Number of pages11
JournalMultiple Sclerosis Journal
Issue number14
Publication statusPublished - Dec 2023

External IDs

PubMed 37776101
ORCID /0000-0003-2465-4909/work/150328294


Sustainable Development Goals

ASJC Scopus subject areas


  • B-cell response, Multiple sclerosis, SARS-CoV-2 vaccination, T-cell response, disease-modifying therapies, sphingosine 1-phosphate receptor modulators, Humans, Vaccination, Antibodies, Viral, Sphingosine 1 Phosphate Receptor Modulators, Multiple Sclerosis, SARS-CoV-2, COVID-19 Vaccines, Sphingosine-1-Phosphate Receptors, COVID-19/prevention & control, Longitudinal Studies