Herpes Simplex Virus Types Not Associated With Increased Risk of Multiple Sclerosis

Ahmed Z. Obeidat, MD, PhD

Data from a cross-sectional, single-center, cohort study showed a significantly higher presence of Epstein-Barr virus (EBV) among patients with multiple sclerosis (MS) compared with controls but no difference in the frequency of herpes simplex virus types 1 and 2 (HSV1 and HSV2).¹ The findings, presented at the 2022 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, June 1-4, in National Harbor, Maryland, come just months after a study of more than 10 million young adults further suggested that EBV is the leading cause of MS.²

Senior author Ahmed Z. Obeidat, MD, PhD, assistant professor of neurology, neuroimmunology and MS, and director of neuroimmunology, Medical College of Wisconsin, and colleagues conducted a retrospective review of clinical serologic data from patients with MS and neurologic controls without MS between July 2018 and December 2021. The investigators assessed frequency of positive immunoglobulin (IgG) on EBV specific simplex viruses such as EBV capsid antigen (EBVCA), EBNA, HSV1, or HSV2.

At the conclusion of the analysis, serum IgG positivity for EBVCA was confirmed in 105 of 106 patients with MS (99.1%) vs 90 of 103 for those without (87.4%; P <.0008). Furthermore, serum EBNA IgG, tested in 100 patients (45 with MS, 55 without) was confirmed in almost all patients with MS (97.8%) and in slightly fewer patients without the disease (83.6%)(P = .02).

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The results for simplex virus types were slightly different, with the confirmed seropositivity of HSV1 similar for patients with (54 of 116; 46.6%) and without MS (54 of 115; 47.0%; P = 0.95). Similarly, serum HSV2 IgG, tested in 233 patients (117 with MS, 116 without MS), was seropositivity confirmed in 27 patients with MS (23.1%) vs 33 without MS (28.4%; P = 0.35).

The link between MS and EBV is not a newfound concept; however, results by Albert Ascherio, MD, DrPH, et al in January 2022 further confirmed that theory.² By collecting data on more than 10 million young adults on activity duty in the US military, he and colleagues found a 32-fold increased risk of developing MS for those infected with the virus, with no increase observed after infection from other viruses, including the similarly transmitted cytomegalovirus. Notably, among the 801 MS cases, only 1 individual was EBV-negative at last blood collection, which took place a median of 1 year before MS onset.

Recently, the National Institute of Allergy and Infectious Disease, part of the National Institutes of Health, announced a new phase 1 study evaluating an investigational preventive EBV vaccine.³ The early-stage trial will look at the safety and immune response of gp350-Ferritin nanoparticle vaccine with a saponin-based Matrix-M adjuvant in a cohort of 40 healthy volunteers. The vaccine, developed by the Laboratory of Infectious Diseases in collaboration with NIAID’s Vaccine Research Center, is designed to target EBV glycoprotein gp350, which is found on the surface of the virus and virus-infected cells.

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REFERENCES
1. Zehms J, Porwal MH, O’Dell S, Finnessy D, Salter A. Epstein-Barr virus, but not herpes simplex virus is associated with multiple sclerosis. Presented at: CMSC Annual Meeting; June 1-4, 2022; National Harbor, MD. Abstract
2. Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. Published online January 13, 2022. doi:10.1126/science.abj82223. NIH launches clinical trial of Epstein-Barr virus vaccine. News release. National Institutes of Health. May 6, 2022. Accessed June 1, 2022. https://www.nih.gov/news-events/news-releases/nih-launches-clinical-trial-epstein-barr-virus-vaccine