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Review
. 2025 Jul;31(8):905-915.
doi: 10.1177/13524585251340812. Epub 2025 May 26.

The path to prevention of multiple sclerosis: Considerations for Epstein-Barr virus vaccine-based prevention studies

Affiliations
Review

The path to prevention of multiple sclerosis: Considerations for Epstein-Barr virus vaccine-based prevention studies

Gregory K Zane et al. Mult Scler. 2025 Jul.

Abstract

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.

Keywords: Epstein-Barr virus (EBV); MS prevention; multiple sclerosis (MS); post-licensure studies; study design; vaccine effectiveness.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: G.K.Z. completed an internship with Merck and Co., Inc. from June 2024 to August 2024, unrelated to the submitted work. G.G. has received compensation, in the last 2 years, for serving as a consultant or speaker or research support from Astoria Biologica, Aurinia Pharmaceuticals, Biogen, BMS-Celgene, BioNTech, GlaxoSmithKline, Janssens/J&J, Japanese Tobacco, Kiniksa, Merck KGaA/EMD Serono, Moderna, Novartis, Sandoz, Sanofi, Roche/Genentech, UCB, Vir Biotechnology, Viracta, and Zenas BioPharma. E.M.M. has received research funding from Biogen and Roche/Genentech; royalties from UpToDate; honoraria for educational content for WebMD; and has consulted for BeCareLink, LLC. J.I.C. is named as an inventor on patent applications for EBV vaccines which have been filed by the National Institutes of Health. A.S., A.B., M.R.H., S.E.H., S.J., B.B., and R.C.P. have no conflicts of interest to report.

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