As a new longitudinal study shows a definitive connection between the Epstein-Barr virus and multiple sclerosis, research turns to vaccines, new treatments — and the further roots of what causes the disease.
Todd, 39, an attorney, had been active and fit his entire life. When he started feeling extreme fatigue and unusual pains, he assumed it was a combination of approaching middle age and parenting a rambunctious toddler during a pandemic. As his symptoms got worse, he pushed for more answers. Ultimately, Todd was diagnosed with multiple sclerosis.
“My doctors have been very optimistic, but it’s been hard to see it from my particular perspective,” Todd says.
However, new research released shortly after Todd’s diagnosis may unlock a key clue for future MS treatment and even prevention. In a longitudinal analysis published in Science in January, researchers found that the Epstein-Barr virus (EBV) is likely one cause of MS, especially in people whose EBV developed into full-blown mononucleosis — people like Todd, whose case of mono in high school was so severe that he was briefly hospitalized.
What the Research Shows
Scientists have long suspected that EBV was connected to MS, but since an overwhelming 95% of the population contracts EBV by young adulthood and only a handful develop MS, it hasn’t been feasible to conduct a randomized trial. For this study, researchers partnered with the U.S. Armed Forces to study serum collected over 20 years from over 10 million young servicepeople, 955 of whom developed MS while in service. (Enlistees are screened for HIV every two years, and the samples are archived.)
The researchers compared three serum samples from 801 people who developed MS and matched each to two randomly selected personnel who did not develop MS but were the same age, sex and race or ethnicity. The pairings also considered the branch of military service, dates when the blood was collected, and whether the members were on active duty. The samples were also screened for evidence of cytomegalovirus (CMV), another herpes virus primarily transmitted through saliva.
Results showed that after EBV infection, risk of developing MS was 32 times greater, but there was no increase after CMV. Additionally, only EBV seroconversion increased neurofilament light chain serum levels, a biomarker of neuroaxonal degeneration.
“Collectively, these findings strongly suggest that the occurrence of EBV infection, detectable by the elicited immune response, is a cause and not a consequence of MS,” the study concludes.
The Future of Treatment
Already, anti-CD20 monoclonal antibodies are one of the most potent treatments for MS. The antibodies deplete the primary site of the latent EBV virus, circulating memory B cells.
“There may be therapeutic approaches to block the virus from spreading once there’s an infection,” says Mark Allegretta, PhD, Vice President of Research, National Multiple Sclerosis Society. “If you look at models such as hepatitis C, there have been drugs that have been developed to prevent the spread of hepatitis C in an individual, and those are very effective. But the challenge for Epstein-Barr virus is that it does establish a latent infection. So it has a latent phase and a lytic phase, and it’s very active in the lytic phase, but essentially in the latent phase, it’s working to hide itself from the immune system. So designing an approach where a drug would block viral replication may be challenging in this case.”
Could an EBV Vaccine Prevent MS?
Moderna has already started a clinical trial for a vaccine to protect against infectious mononucleosis (and thus, EBV). Other trials are likely coming soon. Moderna’s trial is in phase 1 and is currently enrolling people ages 18 to 30. Because so many people develop EBV as children, the ultimate hope is for a vaccine delivered in early childhood. However, whether a vaccine given that young will ultimately prevent MS is yet to be determined.
“The mRNA technology allows the development of vaccines very quickly now,” says study lead author Alberto Ascherio, MD, DrPH, Professor of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health. “But like the HPV vaccine … it will take several years to demonstrate that the vaccine does reduce the risk of MS.”
Another hope is that a vaccine could prevent MS from developing in people who have latent EBV, working in a similar manner as a shingles vaccine, which strengthens the immune response to prevent reactivation.
Todd finds reason for optimism in all these possibilities, especially when he thinks about his three-year-old child. While MS is not an inherited disease, it can have a genetic risk.
“I would certainly be comfortable with my daughter participating in a clinical trial [for the EBV vaccine],” Todd says. “I’m optimistic about the stuff coming down the pipeline, but meanwhile I’m just trying to just focus on the here and now, and what’s actually available to me.”