{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:29:59Z","timestamp":1791221399820,"version":"4.1.0"},"reference-count":81,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>Recent advancements in our understanding of the association between Epstein-Barr virus (EBV) and multiple sclerosis (MS), along with progress in EBV vaccine development, warrant serious considerations of future EBV vaccine-based MS-prevention studies. The clinical, financial, logistical, and technological considerations for designing and conducting retrospective and\/or prospective prevention studies with the primary objective of evaluating the effectiveness of EBV vaccines in preventing MS and other EBV-associated sequelae are presented here. As implementation of these studies may require hundreds of thousands of participants, millions of dollars, and decades to observe if meaningful reductions in MS incidence occur, alternative approaches using pragmatic phase IV, post-licensure study designs focused on either the prevention of MS or infectious mononucleosis (IM), a common clinical manifestation of EBV infection that has been associated with increased risk of MS, are also explored. Current knowledge gaps in technology, funding, and research that must be addressed for a study protocol to be successfully designed and implemented are also discussed.<\/jats:p>","DOI":"10.1177\/13524585251340812","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:18:57Z","timestamp":1748233137000},"page":"905-915","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["The path to prevention of multiple sclerosis: Considerations for Epstein-Barr virus vaccine-based prevention studies"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7169-3762","authenticated-orcid":false,"given":"Gregory K","family":"Zane","sequence":"first","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle, WA, USA"},{"name":"Strategic Analysis, Research, and Training (START) Center, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6165-6607","authenticated-orcid":false,"given":"Anna","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle, WA, USA"},{"name":"Strategic Analysis, Research, and Training (START) Center, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5766-7012","authenticated-orcid":false,"given":"Amanda","family":"Brumwell","sequence":"additional","affiliation":[{"name":"Strategic Analysis, Research, and Training (START) Center, Seattle, WA, USA"},{"name":"Department of Global Health, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9107-1506","authenticated-orcid":false,"given":"Md Rezaul","family":"Hossain","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle, WA, USA"},{"name":"Strategic Analysis, Research, and Training (START) Center, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3361-6026","authenticated-orcid":false,"given":"Stephen E","family":"Hawes","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle, WA, USA"},{"name":"Strategic Analysis, Research, and Training (START) Center, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9995-1700","authenticated-orcid":false,"given":"Gavin","family":"Giovannoni","sequence":"additional","affiliation":[{"name":"Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M","family":"Mowry","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey I","family":"Cohen","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0941-9169","authenticated-orcid":false,"given":"Bruce","family":"Bebo","sequence":"additional","affiliation":[{"name":"Department of Advocacy, Services, and Research, National Multiple Sclerosis Society, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9893-5856","authenticated-orcid":false,"given":"Rena C","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of Washington, Seattle, WA, USA"},{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA"},{"name":"Division of Infectious Diseases, and Epidemiology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/535738"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.5581\/1516-8484.20110103"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0041-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.11.003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00770-5"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2021.1847642"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2022.103636"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.7189\/jogh.10.010404"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.09.041"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585221075990"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-7230-7_22"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abf3685"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.867918"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11080864"},{"key":"e_1_3_3_17_2","first-page":"171","article-title":"First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen","volume":"84","author":"Gu SY","year":"1995","unstructured":"Gu SY, Huang TM, Ruan L, et al. First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen. Dev Biol Stand 1995; 84: 171\u2013177.","journal-title":"Dev Biol Stand"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.04.008"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/523813"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181b9d918"},{"key":"e_1_3_3_21_2","unstructured":"ClinicalTrials.gov. A Study of an Epstein-Barr Virus (EBV) Candidate Vaccine mRNA-1189 in 12- to 30-Year-Old Healthy Adolescents and Adults https:\/\/clinicaltrials.gov\/study\/NCT05164094 (accessed 2 May 2025)."},{"key":"e_1_3_3_22_2","unstructured":"ClinicalTrials.gov. Safety and immunogenicity of an Epstein-Barr Virus (EBV) gp350-ferritin nanoparticle vaccine in healthy adults with or without EBV infection https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT04645147 (accessed 2 May 2025)."},{"key":"e_1_3_3_23_2","unstructured":"ClinicalTrials.gov. Trial evaluating the immunogenicity and safety of an adjuvanted Epstein-Barr virus (EBV) glycoprotein 350 vaccine in EBV-seronegative persons https:\/\/clinicaltrials.gov\/study\/NCT05683834 (accessed 2 May 2025)."},{"key":"e_1_3_3_24_2","unstructured":"ClinicalTrials.gov. A study of an Epstein-Barr virus (EBV) candidate vaccine mRNA-1195 in 18- to 55-year-old healthy adults https:\/\/clinicaltrials.gov\/study\/NCT05831111?term=NCT05831111&rank=1 (accessed 2 May 2025)."},{"key":"e_1_3_3_25_2","article-title":"Sera from mice vaccinated with Epstein-Barr virus-like particles potently prevent infection of human B cells and epithelial cells in vitro","author":"Goy S","year":"2023","unstructured":"Goy S. Sera from mice vaccinated with Epstein-Barr virus-like particles potently prevent infection of human B cells and epithelial cells in vitro. Santa Clara, CA: World Vaccine Congress West Coast, 2023.","journal-title":"Santa Clara, CA: World Vaccine Congress West Coast"},{"key":"e_1_3_3_26_2","unstructured":"CDC. Epstein-Barr virus laboratory testing. Epstein-Barr virus and infectious mononucleosis 2024 https:\/\/www.cdc.gov\/epstein-barr\/php\/laboratories\/index.html (accessed 21 November 2024)."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens9030226"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1109\/JTEHM.2017.2761764"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-817-1_22"},{"key":"e_1_3_3_30_2","unstructured":"World Health Organization. Guidelines on establishment of virology laboratory in developing countries. New Delhi: WHO regional office for South-East Asia 2009 https:\/\/apps.who.int\/iris\/handle\/10665\/205181 (accessed 21 November 2024)."},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200150"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201645"},{"issue":"3","key":"e_1_3_3_33_2","article-title":"Healthcare expenditure of multiple sclerosis patients in 2013: A nationwide study based on French health administrative databases","volume":"3","author":"Lefeuvre D","year":"2017","unstructured":"Lefeuvre D, Rudant J, Foulon S, et al. Healthcare expenditure of multiple sclerosis patients in 2013: A nationwide study based on French health administrative databases. Mult Scler J Exp Transl Clin 2017; 3(3): 2055217317730421.","journal-title":"Mult Scler J Exp Transl Clin"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1159\/000331043"},{"key":"e_1_3_3_35_2","first-page":"401","article-title":"Exploring the cost-effectiveness of EBV vaccination to prevent multiple sclerosis in an Australian setting","volume":"95","author":"Palmer AJ","year":"2023","unstructured":"Palmer AJ, Zhao T, Taylor BV, et al. Exploring the cost-effectiveness of EBV vaccination to prevent multiple sclerosis in an Australian setting. J Neurol Neurosurg Psychiatry 2023; 95: 401\u2013409.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0233499"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.2165\/00019053-200927020-00004"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/jebm.12525"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.07.008"},{"key":"e_1_3_3_40_2","unstructured":"Nardini C. The ethics of clinical trials. 2014; 8: 387."},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2022.2008243"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2021.11.009"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.887794"},{"key":"e_1_3_3_44_2","first-page":"433","article-title":"The Canadian chronic disease surveillance system: A model for collaborative surveillance","volume":"3","author":"Lix LM","year":"2018","unstructured":"Lix LM, Ayles J, Bartholomew S, et al. The Canadian chronic disease surveillance system: A model for collaborative surveillance. Int J Popul Data Sci 2018; 3: 433.","journal-title":"Int J Popul Data Sci"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30181-8"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12425"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.04.020"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.2807\/ese.17.17.20155-en"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1921"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2018.05.015"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70267-4"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq147"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5407"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585231185258"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30470-2"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007043"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181f44abc"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S314959"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-023-02058-5"},{"issue":"1","key":"e_1_3_3_60_2","article-title":"Use of EHRs data for clinical research: Historical progress and current applications","volume":"3","author":"Nordo AH","year":"2019","unstructured":"Nordo AH, Levaux HP, Becnel LB, et al. Use of EHRs data for clinical research: Historical progress and current applications. Learn Health Syst 2019; 3(1): e10076.","journal-title":"Learn Health Syst"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000203247"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.5812\/jkums.111028"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518797290"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207481"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-4578-y"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102260"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.2307\/3563699"},{"key":"e_1_3_3_68_2","volume-title":"European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)","author":"Montalban X","unstructured":"Montalban X. 2024 revisions of the McDonald criteria. In: European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Riga, 15\u201317 January 2024."},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.102816"},{"key":"e_1_3_3_70_2","unstructured":"Framingham Heart Study 2023 https:\/\/www.framinghamheartstudy.org\/ (accessed 21 November 2024)."},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03201-5"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.15199"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001116"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110362"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ1014"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy312"},{"key":"e_1_3_3_77_2","unstructured":"National Multiple Sclerosis Society. List of current research projects funded by the national MS society sorted by topic\/pathways to cures 2023 www.nationalmssociety.org (accessed 21 November 2024)."},{"key":"e_1_3_3_78_2","unstructured":"Multiple Sclerosis National Institute of Neurological Disorders and Stroke https:\/\/www.ninds.nih.gov\/health-information\/disorders\/multiple-sclerosis (accessed 21 November 2024)."},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61114-4"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamahealthforum.2021.2972"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanhl.2025.100703"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00182-1"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251340812","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13524585251340812","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251340812","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:18:31Z","timestamp":1777695511000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13524585251340812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":81,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1177\/13524585251340812"],"URL":"https:\/\/doi.org\/10.1177\/13524585251340812","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,26]]}}}