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

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.

Déclaration de conflit d'intérêts

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: U.P. received speaker fee from Merck, Biogen, Bayer, and Roche and personal compensation from Biogen, Roche, and Sanofi for consulting service. C.W. received travel support from Novartis. A.D. received personal compensation and travel grants from Sanofi-Aventis, Janssen-Cilag, Biogen, Celgene/Bristol-Myers Squibb, and Roche for speaker activity. T.Z. reports consulting or serving on speaker bureaus for Biogen, Celgene, Roche, Novartis, Celgene Merck, and Sanofi as well as research support from Biogen, Novartis, Merck, and Sanofi. K.A. received personal compensation from Roche, Sanofi, Alexion, Teva, Biogen, and Celgene for consulting service. M.M.-E., G.K.A.R., R.H., M.D., and Y.A. have nothing to disclose.