Anti-SARS-CoV-2 vaccination in differently treated Multiple Sclerosis patients: evaluation of antibody neutralizing activity and T cell response over time

Long lasting immune response to anti-SARS-CoV-2 vaccination in people with Multiple Sclerosis (pwMS) is still largely unexplored. In this study, sera from 24 healthy donors (HD) and 70 pwMS under different treatments or untreated were collected before and up to six months after three doses of vaccine and at each time point different analysis were conducted. ELISA assay was performed to evaluate the titer of antibodies (Ab) directed against the Region Binding Domain of the Spike (S) protein and the neutralization efficacy of Ab was tested by means of a pseudovirion-based neutralization assay. T cell response was analysed by stimulating the Peripheral Blood Mononucleated Cells with a pool of peptides covering the S coding sequence. Overall, vaccination induced comparable levels of IgGs, neutralizing activity and T cell response in HD and in untreated and treated patients. An exception is represented by patients treated with ocrelizumab and fingolimod that showed lower levels of IgGs compared to untreated pwMS; patients under ocrelizumab had also an Ab neutralization ability under the limit of detection. We also observed that the occurrence of a natural infection by SARS-CoV-2 after the third dose of vaccine increased the neutralization capacity and the T cell response in treated pwMS. These findings suggest that ocrelizumab and fingolimod-treated patients are at higher risk of infection and in need of a more careful follow-up after vaccination. These data can also help to better plan an effective vaccination strategy for MS patients.