Does EBV infection even matter?
In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.
Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.
Johns Hopkins Medicine
Dr. Peter Calabresi
Still, he is unconvinced that EBV is solely responsible for MS. “I think it’s hard to draw a straight line between EBV and MS as one might with HPV [human papillomavirus] and cervical cancer. For example, we know that EBV accounts for more than 1% of all cancers, and EBV can also cause other autoimmune diseases such as lupus and Sjogren’s, so it’s complicated. And MS of course has genetic susceptibility that’s not limited to the major histocompatibility complex (MHC) genes that are associated with presenting viral peptides,” said Dr. Calabresi.
Evidence relating MS vulnerability to other genetic and environmental factors, including diet, sunlight, smoking, and even pollution, calls into question a direct causal relationship between EBV and MS, he said.
The age prevalence of EBV would complicate efforts to eradicate it. Seroprevalence is 55% by age 5-11 and 75% among university students. “This is important because the duration of the vaccine response–induced protection in young seronegative children is not lengthy. Vaccinated individuals may become susceptible to natural infection at an age where the consequences of infection are more severe, especially leading to infectious mononucleosis, and hopefully not MS. This then raises the issue of the need for boosters, which we’re all well aware of during the COVID pandemic. This may be a problem, especially in young adults due to noncompliance,” said Dr. Calabresi.
He pointed out that not all vaccine attempts went well. In the 1960s, early respiratory syncytial virus (RSV) vaccines caused enhanced respiratory disease and 2 deaths. “We need to be careful when we think about targeting healthy at-risk young people,” said Dr. Calabresi.
Rather than pursue vaccination, Dr. Calabresi favors research into EBV latency in B cells as well as how EBV-infected B cells may cause or exacerbate MS, with the hopes of developing interventions. “It’s tempting to speculate that the success of the anti-CD 20 monoclonal antibody therapies is related to depletion of EBV infected B cells. In fact, I think that may be the case,” he said.
Dr. Cohen has no relevant financial disclosures. Dr. Calabresi has served on a scientific advisory board or data monitoring board for Biogen and Disarm Therapeutics.