Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination

Orrù, Valeria;Serra, Valentina;Marongiu, Michele;Lai, Sandra;Lodde, Valeria;Zoledziewska, Magdalena;Steri, Maristella;Loizedda, Annalisa;Lobina, Monia;Piras, Maria Grazia;Virdis, Francesca;Delogu, Giuseppe;Marini, Maria Giuseppina;Mingoia, Maura;Floris, Matteo;Masala, Marco;Castelli, M Paola;Mostallino, Rafaela;Frau, Jessica;Lorefice, Lorena;Farina, Gabriele;Fronza, Marzia;Carmagnini, Daniele;Carta, Elisa;Pilotto, Silvy;Chessa, Paola;Devoto, Marcella;Castiglia, Paolo;Solla, Paolo;Zarbo, Roberto Ignazio;Idda, Maria Laura;Pitzalis, Maristella;Cocco, Eleonora;Fiorillo, Edoardo;Cucca, Francesco

2024-01-01

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Abstract

Introduction: 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. Methods: 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. Results and discussion: 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.