Antibodies fighting Epstein-Barr virus could misfire and trigger multiple sclerosis, new study shows
The findings add to growing evidence of a link between the virus and the neurodegenerative condition, adding urgency to the hunt for a vaccine.
- 23 May 2023
- 4 min read
- by Priya Joi
Multiple sclerosis (MS) could be triggered by the misfiring of naturally occurring antibodies against the Epstein-Barr virus (EBV) that most of us are infected with in childhood.
The research, published in Science Advances, suggests that antibodies that our body deploys to fight EBV mistakenly targets a similar looking protein in the brain and spinal cord, which can make the development of MS, an incurable condition in which people develop mobility issues, fatigue and pain, more likely.
The link between EBV and MS is now so strong that prior EBV infection “is a likely prerequisite” for developing MS.
EBV is a common childhood virus and around 90% of us are infected at some point. Often people are asymptomatic, while some develop mononucleosis or glandular fever. In a small proportion, however, this harmless virus is linked to the development of serious illnesses such as cancers, lupus, chronic fatigue syndrome or MS. Why that happens isn't clear: causal links are hard to draw given the ubiquity of EBV in the general population.
The link between EBV and MS is now so strong that prior EBV infection "is a likely prerequisite" for developing MS, according to the Swedish group of authors, including from the The Karolinska Institute, on the Science Advances paper.
Last year a landmark 20-year study of ten million US military personnel showed that those infected with EBV are 32 times more likely to develop MS.
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Epstein-Barr nuclear antigen 1 (EBNA1), which triggers an immune response, looks very similar to alpha-crystallin B (CRYAB), which has a critical role in protecting our central nervous system from inflammation. Thus antibodies our body produces to fight EBV can also mistakenly attack our own proteins.
The researchers analysed blood samples from more than 700 patients with MS and around 700 without MS. They found the cross-reactive antibodies (that could target both proteins) were present in about 23% of MS patients and 7% of controls.
The Epstein-Barr virus turns out to be a master of molecular mimicry as this is not the first time that EBV proteins have resembled critical proteins in our body. Stanford University scientists published fingings in Nature last year showing that antibodies to EBNA1 also bound to a protein made in the brain and spinal cord called the glial cell adhesion molecule or GlialCAM, which is in the protective sheath covering our nerves.
In people whose EBV antibodies are destroying their own protective CRYAB or GlialCAMproteins, it means damage to the nervous systems so that electrical impulses can't travel as easily, leading to numbness, muscle weakness or paralysis, and severe fatigue. The optic nerve can also be affected, leading to blindness.
Although vaccine research had stalled for many years, the recent evidence on the link between EBV and MS and other diseases has caused it to ramp back up.
Although vaccine research had stalled for many years, the recent evidence on the link between EBV and MS and other diseases has caused it to ramp back up. There are now three EBV vaccines in the pipeline.
There are now three EBV vaccines in the pipeline. Moderna is using the mRNA platform it used for its COVID-19 vaccines for EBV in phase 1 clinical trials across the US. The US National Institute of Allergy and Infectious Diseases launched an early-stage clinical trial to evaluate an investigational preventative vaccine, and Hank Balfour, professor of laboratory medicine and pathology at the University of Minnesota, is also working on an EBV vaccine.
Although the road ahead is likely to be a long one, ultimately the goal would be to vaccinate children against EBV. The mechanisms by which EBV can cause severe disease in some but not others is not entirely understood. What is clear, in the words of Hank Balfour, is that "it's much better not to get infected at all".
