{"doi":"10.3389/fimmu.2024.1416464","title":"Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination","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.","journal":"Frontiers in Immunology","year":2024,"id":465941,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8795,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":218095,"name":"Valentina Serra","orcid":"0000-0002-5782-8752","position":1,"is_corresponding":false},{"id":218094,"name":"Michele Marongiu","orcid":"0000-0002-7289-9815","position":2,"is_corresponding":false},{"id":218098,"name":"Sandra Lai","orcid":"0000-0003-4198-9989","position":3,"is_corresponding":false},{"id":249141,"name":"Valeria Lodde","orcid":"0000-0001-6904-1431","position":4,"is_corresponding":false},{"id":55374,"name":"Magdalena Żołędziewska","orcid":"0000-0002-3033-6133","position":5,"is_corresponding":false},{"id":55363,"name":"Maristella Steri","orcid":"0000-0001-5869-3872","position":6,"is_corresponding":false},{"id":218106,"name":"Annalisa Loizedda","orcid":"0000-0002-9749-5905","position":7,"is_corresponding":false},{"id":218102,"name":"Monia Lobina","orcid":"0000-0003-3620-3160","position":8,"is_corresponding":false},{"id":218101,"name":"Maria Grazia Piras","orcid":"0000-0001-9004-0900","position":9,"is_corresponding":false},{"id":218100,"name":"Francesca Virdis","orcid":"0000-0002-4151-4257","position":10,"is_corresponding":false},{"id":1297336,"name":"Giuseppe Delogu","orcid":"0000-0002-6128-9835","position":11,"is_corresponding":false},{"id":1297337,"name":"M. Marini","orcid":"0000-0003-0371-9398","position":12,"is_corresponding":false},{"id":1297338,"name":"Maura Mingoia","orcid":"0000-0003-3716-241X","position":13,"is_corresponding":false},{"id":218109,"name":"Matteo Floris","orcid":"0000-0003-4385-9336","position":14,"is_corresponding":false},{"id":533390,"name":"Marco Masala","orcid":"0000-0001-5556-9964","position":15,"is_corresponding":false},{"id":262919,"name":"M. Paola Castelli","orcid":"0000-0003-3249-4706","position":16,"is_corresponding":false},{"id":1297767,"name":"Rafaela Mostallino","orcid":null,"position":17,"is_corresponding":false},{"id":644439,"name":"Jessica Frau","orcid":"0000-0001-9068-9144","position":18,"is_corresponding":false},{"id":1243483,"name":"Lorena Lorefice","orcid":"0000-0003-2050-2908","position":19,"is_corresponding":false},{"id":1297339,"name":"Gabriele Farina","orcid":"0000-0002-2339-6939","position":20,"is_corresponding":false},{"id":1297340,"name":"Marzia Fronza","orcid":"0000-0002-1153-5866","position":21,"is_corresponding":false},{"id":1297768,"name":"Daniele Carmagnini","orcid":null,"position":22,"is_corresponding":false},{"id":1297769,"name":"Elisa Carta","orcid":null,"position":23,"is_corresponding":false},{"id":1297341,"name":"Silvy Pilotto","orcid":"0000-0001-7950-0136","position":24,"is_corresponding":false},{"id":1297770,"name":"Paola Chessa","orcid":null,"position":25,"is_corresponding":false},{"id":85476,"name":"Marcella Devoto","orcid":"0000-0002-4431-5114","position":26,"is_corresponding":false},{"id":1297342,"name":"Paolo Castiglia","orcid":"0000-0002-0972-4828","position":27,"is_corresponding":false},{"id":761768,"name":"Paolo Solla","orcid":"0000-0002-2982-0665","position":28,"is_corresponding":false},{"id":1297771,"name":"Roberto Ignazio Zarbo","orcid":null,"position":29,"is_corresponding":false},{"id":249140,"name":"Maria Laura Idda","orcid":"0000-0001-5243-8977","position":30,"is_corresponding":false},{"id":218104,"name":"Maristella Pitzalis","orcid":"0000-0003-4975-6987","position":31,"is_corresponding":false},{"id":289311,"name":"Eleonora Cocco","orcid":"0000-0002-3878-8820","position":32,"is_corresponding":false},{"id":14683,"name":"Edoardo Fiorillo","orcid":"0000-0002-8690-4988","position":33,"is_corresponding":false},{"id":14679,"name":"Francesco Cucca","orcid":"0000-0002-7414-1995","position":34,"is_corresponding":false},{"id":14664,"name":"Valeria Orrù","orcid":"0000-0002-6047-4625","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:04:50.328230Z","pmid":"39076966","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}