Demystifying Multiple Sclerosis Etiology: Molecular Mimicry and The Role of Epstein-Barr Virus - Episode 9
Bridget A. Bagert, MD, leads a discussion on the ideal patient populations for using a potential vaccine for multiple sclerosis, and the panel comments on other factors to consider when administering vaccines.
Scott Newsome, DO: Bridget, I’m going to put you on the spot. Not that there’s a right or wrong answer. Let’s say we have only 1 opportunity to use a vaccine within MS [multiple sclerosis], at least early on. Which patient population would you give this to based on all that we’ve talked about? You hinted at some of this. You talked about B-cell follicles and those things. What would you go for? Would you do progressive MS or relapsing MS? I’d be interested to hear your thoughts.
Bridget A. Bagert, MD: It’s an interesting question and, of course, very speculative. I’d target newly diagnosed patients or those with CIS [clinically isolated syndrome] to see if we can change the arc of the future because we kind of know what their future holds. There are enough natural history data. We know what happens in some of these patients. That would be tremendously impactful if we could stop it from progressing and stop that process—stop progressive MS, stop the accumulation of B cells in the brain later that we understand to be progressive MS. That’s what I would do. It’s very tempting to think about doing it also in progressive multiple sclerosis. There’s so much biological abnormality to address and to be undone that I wonder if we’d be setting ourselves up for negative studies.
Scott Newsome, DO: That’s a good thought. As you were going through it, you swayed my initial thoughts. I was like, “Progressive MS is such a huge unmet need.” We don’t really have any therapies. The few we consider are potentially B-cell depletion in progressive disease. You made very strong points, changing the arc.
Bridget A. Bagert, MD: Just to add 1 comment, for the EBV [Epstein-Barr virus]–specific CD8 T-cell therapies, those trials are going on, and those populations are in progressive forms of MS. That’s very promising and based on Michael Pender’s hypothesis and the whole EBV theory of MS. There’s a lot of hope there. It’s very early, but there’s a lot to be excited about. We can go back to the hypothetical if you want.
Scott Newsome, DO: Obviously, we’d love to try it in all subtypes. If you hit on 1, it’s going to be huge. I don’t know what others feel.
Ahmed Obeidat, MD, PhD: I’ll add 1 thing about vaccination. One question I want to pose is, do we worry about molecular mimicry as we think about the vaccine? We heard about the proteins GlialCAM and EBNA1. Are we worried that certain parts of the vaccine might actually trigger MS?
Lawrence Steinman, MD: In the Alberto Ascherio study, the top hit in the supplementary table 1 was the region on EBNA1. Right below is an envelope protein. We have to be aware that a vaccine could worsen the disease. This raises another point. We’re exceptionally spoiled with what happened during Operation Warp Speed and the dramatic success of the COVID-19 vaccines. These vaccines will be much more on this trajectory of typical vaccine development. It’s going to take a decade or more under the best of conditions. The development of the measles vaccine and the HPV [human papillomavirus] vaccines are going to be a much more realistic model. We had an exceptional situation and exceptional success, but it’s not going to happen again soon unless there’s another emergency pandemic. EBV is almost the antithesis of that.
We have to look at the history of the development of the polio vaccine. Amit Bar-Or is sitting near 1 of the points that you could call ground zero: the Wistar Institute in Philadelphia, Pennsylvania. They had a competing polio vaccine from Hilary Koprowski, but even that 1—with known periodic summertime epidemics of the GI [gastrointestinal] virus—the initial trials began in the late 1940s. Jonas Salk had a big breakthrough, but it still took about 5 years, and there was a lot of attention put on it. To answer to the question about which type of MS I’d treat first, I think one would have to do individual studies with all the different types.
One other thing, just as to throw out ideas, I’d always worried that MS wasn’t a coherent disease because Jean-Martin Charcot and others identified the disease and gave it a name. In Alberto’s data, in the Harvard study, you have numbers like 800 of 801, given this diagnosis of MS, were positive for EBV. And 34 of 35 developed serology before they had MS. Now I believe that whatever guessing Charcot and others were doing, they did find a coherent disease. I don’t know if the subtypes are going to be that coherent, but let’s be optimistic.
Transcript Edited for Clarity