EBV and Multiple Sclerosis: From Causality to Vaccines and Immunotherapy

EBV and Multiple Sclerosis: From Causality to Vaccines and Immunotherapy

Prepared by the Hesperion Research Team For decades, researchers suspected that Epstein–Barr virus (EBV) might play a role in multiple sclerosis (MS). EBV infects more than 90% of the world’s population, usually without serious consequences. But in 2022 a landmark longitudinal study established EBV as a causal risk factor for MS, showing that EBV infection increased the risk of developing MS more than 30-fold. In the past two years, this discovery has transformed MS research, with vaccine programs and targeted immunotherapies now in development.

1) Establishing Causality

A massive cohort study of U.S. military personnel (Bjornevik et al., Science, 2022) followed over 10 million individuals. Those who seroconverted for EBV during service had dramatically higher risk of later developing MS, while no similar link was seen for other viruses. This made EBV the strongest known environmental risk factor for MS and solidified its causal role.

2) Vaccines Against EBV

Since then, vaccine development has accelerated:

• mRNA-1189 (Moderna): An mRNA vaccine encoding EBV glycoproteins entered early clinical testing in 2023, with updates in 2024–2025 showing favorable safety and immunogenicity profiles. Trials are ongoing to see whether vaccination can prevent primary EBV infection.
• Other candidates: Viral vector and protein-subunit vaccines are being explored in parallel, some designed specifically for MS prevention trials.

While it will take years to prove whether EBV vaccination prevents MS, these programs represent the first serious attempt at primary prevention of an autoimmune disease.

3) EBV-Targeted Immunotherapy

• EBV-specific T cells: Adoptive immunotherapy trials are underway in progressive MS, expanding autologous or donor T cells to target EBV-infected B cells in the CNS.
• Antivirals: Traditional antivirals against EBV have not yet shown robust benefit in MS, but next-generation inhibitors are in development.
• Monoclonal antibodies: Strategies include antibodies against EBV entry proteins to block reinfection or reactivation.

4) Clinical Implications

• Risk prediction: Virtually all MS patients are EBV-positive, suggesting EBV is necessary but not sufficient for disease — genetics and other environmental factors modify risk.
• Prevention horizon: If EBV vaccination proves effective, MS could become the first autoimmune disease with a preventive vaccine strategy.
• Therapeutic innovation: EBV-targeted immunotherapies could benefit patients with progressive MS, where current treatments are limited.

5) Hesperion’s Perspective

• EBV research illustrates how infection triggers and autoimmunity can intersect.
• We track EBV vaccine and immunotherapy trials closely, as they may shift MS care from symptom management to causal intervention.
• Integrating EBV serostatus and viral activity markers into endotype mapping could help refine MS subtypes and treatment response.

Conclusion

The link between EBV and MS has moved from hypothesis to proof. Vaccines and EBV-specific therapies now offer the possibility of both preventing and treating MS in fundamentally new ways. If successful, these strategies could transform not just MS care, but the entire field of autoimmunity by showing how targeting a viral trigger can modify chronic disease.