%0 Journal Article
%T Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination.
%A Orrù V
%A Serra V
%A Marongiu M
%A Lai S
%A Lodde V
%A Zoledziewska M
%A Steri M
%A Loizedda A
%A Lobina M
%A Piras MG
%A Virdis F
%A Delogu G
%A Marini MG
%A Mingoia M
%A Floris M
%A Masala M
%A Castelli MP
%A Mostallino R
%A Frau J
%A Lorefice L
%A Farina G
%A Fronza M
%A Carmagnini D
%A Carta E
%A Pilotto S
%A Chessa P
%A Devoto M
%A Castiglia P
%A Solla P
%A Zarbo RI
%A Idda ML
%A Pitzalis M
%A Cocco E
%A Fiorillo E
%A Cucca F
%J Front Immunol
%V 15
%N 0
%D 2024
%M 39076966
%F 8.786
%R 10.3389/fimmu.2024.1416464
%X <B>UNASSIGNED: </B>Disease-modifying therapies (DMTs) have been shown to improve disease outcomes in multiple sclerosis (MS) patients. They may also impair the immune response to vaccines, including the SARS-CoV-2 vaccine. However, available data on both the intrinsic immune effects of DMTs and their influence on cellular response to the SARS-CoV-2 vaccine are still incomplete.<BR><B>UNASSIGNED: </B>Here, we evaluated the immune cell effects of 3 DMTs on the response to mRNA SARS-CoV-2 vaccination by comparing MS patients treated with one specific therapy (fingolimod, dimethyl fumarate, or natalizumab) with both healthy controls and untreated patients. We profiled 23 B-cell traits, 57 T-cell traits, and 10 cytokines, both at basal level and after stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS patients, treated with DMTs or untreated, and 32 healthy controls. Measurements were made before vaccination and at three time points after immunization.<BR><B>UNASSIGNED: </B>MS patients treated with fingolimod showed the strongest immune cell dysregulation characterized by a reduction in all measured lymphocyte cell classes; the patients also had increased immune cell activation at baseline, accompanied by reduced specific immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike specific B cells progressively increased over the three time points after vaccination, even when antibodies measured from the same samples instead showed a decline. Our findings demonstrate that repeated booster vaccinations in MS patients are crucial to overcoming the immune cell impairment caused by DMTs and achieving an immune response to the SARS-CoV-2 vaccine comparable to that of healthy controls.