27 January 2022

Epstein-Barr Virus a ‘leading cause’ of MS

Clinical

A study of 10 million adults suggests a vaccine against EBV could one day help prevent MS.


People infected with Epstein-Barr Virus (EBV) appear to have a 32-fold higher chance of developing multiple sclerosis (MS), raising hope that a vaccine could help prevent the chronic, demyelinating disease.  

The link between the two conditions has been challenging to study, because EBV infection is extremely common while MS is rare. 

For this study, researchers analysed serum regularly collected from a cohort of 10 million young adults serving in the US military over a 20-year period. Out of this enormous sample, only 955 were diagnosed with MS during their service. Of the 801 who had serum samples that could be tested for EBV infection, all but one was found to have had EBV at the onset of their MS. 

In contrast, among the small control group of 90 individuals who weren’t infected with EBV at the start of the study nor developed MS, only 51 later became infected with EBV.  

These figures suggest the chances of developing MS are more than 30 times higher after an EBV infection.  

“These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS,” the authors wrote in Science

Their analysis of cytomegalovirus antibodies found no indication that any environmental, behavioural or personal factors increased an individual’s susceptibility to both conditions. The researchers also excluded the possibility that immune dysregulation was making people more susceptible to infections generally in the early and pre-clinical phase of MS. 

Sydney MS expert Professor Michael Barnett, director of RPA Hospital’s MS Clinic, said that while the link between MS and EBV had been long suggested, this massive study was “far more convincing than most”. 

“It’s certainly the strongest evidence from an epidemiological perspective simply because of the size of the data set. It’s such a vast data set,” he told TMR

But Professor Barnett did not agree with the author’s suggestion that EBV was a leading cause of MS. Instead, he said it may show the infection was an obligate step in a multi-step causation of the chronic condition.  

“There might be genetic background, the individual EBV infection, and then a whole series of potential other factors that increase the risk of MS. But if you haven’t had EBV infection, then the other ones don’t really matter,” he explained. 

While this study did not sufficiently prove that the infection was an obligate step, such a finding would have important implications for therapy. It could spell treatments that targeted EBV-infected immune cells, antiviral therapies and vaccination in early childhood when most EBV infections occurred. 

Nevertheless, the findings weren’t likely yet to change clinical practice, said Professor Barnett.  

“Right now, there are a multitude of therapies on the market for MS,” he said. “One of the most powerful classes is the B cell depleting therapies, and they target specifically memory B cells, one arm of the immune system. 

“Interestingly, EBV resides permanently in those memory B cells,” he added. “The therapies we’ve got now basically wipe out all your B cells. They’re agnostic to whether the B cell has EBV in it or not. And they work.” 

But he said we wouldn’t know for sure whether the reason they work is because they knock out EBV-infected cells until more targeted therapies are developed. 

“There are ongoing clinical trials, including in Australia, of therapies that find and destroy EBV-infected B cells. When we get the results of those studies, that will be a little more interesting.” 

A vaccine for EBV had not been a priority, Professor Barnett noted, because although up to 95% of the population were infected, it usually caused only very mild disease. 

“But if we are to develop the vaccine based on this sort of data, and it’s an obligate step, vaccination could have a dramatic impact on the prevalence of MS, which currently affects about 25,000 Australians, and millions of people worldwide,” he said. 

“I hope they’re right.” 

Science 2022, online 13 January