Could an Epstein-Barr Virus (EBV) Vaccine Help Prevent Multiple Sclerosis (MS)?

Multiple sclerosis (MS) is an autoimmune disease in which a type of immune cell, called a T cell, attacks the myelin (the protective covering around nerves) in the brain and spinal cord, leading to a variety of physical and neurological symptoms that progress over time.

But what causes MS, exactly? Even though experts believe that genetic and environmental factors, including exposure to tobacco smoke, obesity, high salt intake, and lack of sunlight, increase an individual’s risk of developing MS, whether there is a necessary environmental trigger is unknown. For years, researchers have suspected that Epstein-Barr virus (EBV) has had a role in the onset of MS, but studies have not shown a cause and effect.

We spoke with David Hafler, MD, an MS expert and chair of the Department of Neurology at Yale School of Medicine, to learn more about the potential connection between EBV and MS and what that link could mean for future MS treatments.

EBV is a type of herpes virus that's highly contagious and spreads primarily through saliva. It can be transmitted by sharing drinks, utensils, or food. While exposure to EBV is common and generally harmless, with about 90% of adults having been exposed to it, it can cause mononucleosis, or mono, especially when contracted during adolescence or young adulthood. Most people who are infected with EBV don’t know that it’s happening, because they either have no symptoms or the symptoms mimic other common, mild conditions. Once an individual has been infected by EBV, however, it remains inactive in the body.

For quite some time, there's been a suspicion in the medical community that EBV might play a role in the chain of events leading to MS, especially because nearly all MS patients have been infected with EBV. A recent study by Ascherio and colleagues published in Science showed that individuals were significantly more likely to develop MS after being infected with EBV. They conducted a longitudinal analysis of over 10 million subjects where EBV infection was followed by the initiation of MS in a subset of individuals. While 93% of the general population has been exposed to EBV without developing MS, the strong correlation in MS patients suggests that EBV could be a significant environmental factor for those with a genetic predisposition to MS.

Additionally, the dramatic clinical and immune responses found with B cell depletion in MS and our observation that there was an enrichment of causative single nucleotide polymorphisms, or SNPs [DNA sequence variations], in enhancers in B cells specific to MS patients raises the hypothesis that EBV infection of B cells in genetically susceptible hosts triggers abnormal immune modulation, leading to the activation of pathogenic T cells and contributing to MS pathogenesis [the process by which a disease develops].

MS is a complex genetic disease believed to be caused by a combination of hundreds of common genetic variants and environmental factors. Unlike diseases caused by a single gene mutation, such as muscular dystrophy and sickle cell anemia, MS involves hundreds of genetic variants, each with a small effect. When someone with some or all of these genetic factors contracts EBV, it may set the stage for MS, particularly if other environmental factors come into play, such as smoking, obesity, a high-salt diet, and cumulative exposure to sunlight. MS is more common among people who live in countries in the northern and southern hemispheres that are farthest away from the equator, where people receive less sunlight.

We're conducting extensive research to better understand MS and its potential link to EBV. For example, the DREAM [Detection Research of Early Asymptomatic MS] study, led by my colleague Erin Longbrake, MD, PhD, aims to identify early signs of MS by studying relatives of MS patients. There is a slight increase in the risk of these relatives developing MS, but it isn’t a highly inheritable disease. Still, Dr. Longbrake and her team are hoping to find out whether it’s possible to identify MS before symptoms arise. Researchers will also look for the presence of EBV infection in study participants’ blood samples.

Additionally, we're exploring the development of an EBV vaccine, which could potentially prevent MS if the link is confirmed. There's also research into therapeutic vaccines that could help MS patients by targeting EBV-infected B cells that might be contributing to the disease.

If we can confirm that EBV is a cause of MS, an EBV vaccine could dramatically reduce the incidence of MS, much like how other vaccines have nearly eliminated diseases like measles and polio in the U.S. The idea is to vaccinate children before they're exposed to EBV, which could potentially prevent MS from developing in those genetically predisposed to it.