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Medicine

New 'Inverse Vaccine' Shows Potential to Treat MS and Other Autoimmune Diseases (uchicago.edu) 73

Posted by EditorDavid from the taking-a-shot dept.
This week saw an announcement from the University of Chicago's Pritzker School of Molecular Engineering. A new type of vaccine "has shown in the lab setting that it can completely reverse autoimmune diseases like multiple sclerosis and type 1 diabetes — all without shutting down the rest of the immune system." A typical vaccine teaches the human immune system to recognize a virus or bacteria as an enemy that should be attacked. The new "inverse vaccine" does just the opposite: it removes the immune system's memory of one molecule. While such immune memory erasure would be unwanted for infectious diseases, it can stop autoimmune reactions like those seen in multiple sclerosis, type I diabetes, or rheumatoid arthritis, in which the immune system attacks a person's healthy tissues. The inverse vaccine, described in Nature Biomedical Engineering, takes advantage of how the liver naturally marks molecules from broken-down cells with "do not attack" flags to prevent autoimmune reactions to cells that die by natural processes. Pritzker School of Molecular Engineering researchers coupled an antigen — a molecule being attacked by the immune system — with a molecule resembling a fragment of an aged cell that the liver would recognize as friend, rather than foe. The team showed how the vaccine could successfully stop the autoimmune reaction associated with a multiple-sclerosis-like disease...

Jeffrey Hubbell [lead author of the new paper] and his colleagues knew that the body has a mechanism for ensuring that immune reactions don't occur in response to every damaged cell in the body — a phenomenon known as peripheral immune tolerance, which is carried out in the liver. They discovered in recent years that tagging molecules with a sugar known as N-acetylgalactosamine (pGal) could mimic this process, sending the molecules to the liver where tolerance to them develops. "The idea is that we can attach any molecule we want to pGal and it will teach the immune system to tolerate it," explained Hubbell. "Rather than rev up immunity as with a vaccine, we can tamp it down in a very specific way with an inverse vaccine."

In the new study, the researchers focused on a multiple-sclerosis-like disease in which the immune system attacks myelin, leading to weakness and numbness, loss of vision and, eventually mobility problems and paralysis. The team linked myelin proteins to pGal and tested the effect of the new inverse vaccine. The immune system, they found, stopped attacking myelin, allowing nerves to function correctly again and reversing symptoms of disease in animals. In a series of other experiments, the scientists showed that the same approach worked to minimize other ongoing immune reactions...

Initial phase I safety trials of a glycosylation-modified antigen therapy based on this preclinical work have already been carried out in people with celiac disease, an autoimmune disease that is associated with eating wheat, barley and rye, and phase I safety trials are under way in multiple sclerosis. Those trials are conducted by the pharmaceutical company Anokion SA, which helped fund the new work and which Hubbell cofounded and is a consultant, board member, and equity holder. The Alper Family Foundation also helped fund the research.

"There are no clinically approved inverse vaccines yet, but we're incredibly excited about moving this technology forward," says Hubbell.
Thanks to Slashdot reader laughingskeptic for sharing the news.
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New 'Inverse Vaccine' Shows Potential to Treat MS and Other Autoimmune Diseases More

New 'Inverse Vaccine' Shows Potential to Treat MS and Other Autoimmune Diseases

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  • These have been researched for decades (Score:5, Insightful)

    by backslashdot ( 95548 ) on Saturday September 16, 2023 @10:47AM (#63853298)

    They're also called tolerizing or tolerogenic vaccines. Here's an example from 2006: https://med.stanford.edu/conte... [stanford.edu]

    Here's a review: https://www.frontiersin.org/ar... [frontiersin.org]

    • Re: (Score:2, Informative)

      by AmiMoJo ( 196126 )

      This could be game changing for people like me with auto-immune problems, but I have a feeling that by the time it's available most of my life will be over. I wish there was some way for people to get this stuff, pay for it, with the understanding that it's still in development.

      Maybe for people with diagnosed auto-immune conditions and the agreement of their doctor?

      • Re: (Score:2)

        by HiThere ( 15173 )

        Well, my guess at the timeline (outsider...no real relevant info) is a decade or so. There *WILL* be problems during development. People always tend to ignore that in their time estimates. https://www.techtarget.com/wha... [techtarget.com]

      • I would love that. Majority of the targets are death sentences with a pretty poor quality of life during that time. I canâ(TM)t be the only person whoâ(TM)s be willing to try. Best case it works worst case I speed along my demise and perhaps help them perfect it for next person.

      • Re: (Score:2)

        by dgatwood ( 11270 )

        This could be game changing for people like me with auto-immune problems, but I have a feeling that by the time it's available most of my life will be over. I wish there was some way for people to get this stuff, pay for it, with the understanding that it's still in development.

        Well, if you want to try a shortcut that probably won't help but is unlikely to hurt you, N-acetylglucosamine (an isomer of the substance involved) is available over the counter as a dietary supplement, as is phosphatidylserine (which likely has similar properties). You might try taking those two supplements and seeing if either or both makes any difference.

        My guess is that because those substances won't be in any way attached to the molecule that your immune system is reacting to, it probably *won't* help

    • Re: (Score:3)

      by dgatwood ( 11270 )

      They're also called tolerizing or tolerogenic vaccines. Here's an example from 2006: https://med.stanford.edu/conte... [stanford.edu]

      Here's a review: https://www.frontiersin.org/ar... [frontiersin.org]

      The paper you linked, if my skimming is correct, consisted of using a DNA vaccine to causing your body's cells to produce more of a protein so that your immune system exhausts itself trying to fight it and gives up. It's a bit like using drops of liquid containing pollen in suspension under your tongue to reduce allergic responses. That approach can work, but if my experience with allergy desensitization is any indication, I'd expect the desensitization to take months (or years), and to just reduce its se

      • The approach in this paper actually combines the antigen with a protein that your immune system knows not to attack.

        Yes, that's called a tolerizing adjuvant -- also a decades old idea: https://pubmed.ncbi.nlm.nih.go... [nih.gov] I think the review paper I linked above mentions that technique too. Of course finding a good one is a big deal, if pGal works that's great.

        I'm not saying that paper isn't an advance, it's good btw. My point was to show that it's building on a lot of work. I'm not against it, it's one of a few promising techniques to induce specific tolerance. And yeah they're making progress. I just hope all the ideas g

        • Re: (Score:2)

          by dgatwood ( 11270 )

          The approach in this paper actually combines the antigen with a protein that your immune system knows not to attack.

          Yes, that's called a tolerizing adjuvant -- also a decades old idea: https://pubmed.ncbi.nlm.nih.go... [nih.gov] I think the review paper I linked above mentions that technique too. Of course finding a good one is a big deal, if pGal works that's great.

          I'm not saying that paper isn't an advance, it's good btw. My point was to show that it's building on a lot of work. I'm not against it, it's one of a few promising techniques to induce specific tolerance. And yeah they're making progress. I just hope all the ideas get the work and funding needed. We'd be here faster if that had happened.

          +1. So many promising ideas with successful mouse testing never make it to human trials.

  • antivax (Score:5, Funny)

    by bugs2squash ( 1132591 ) on Saturday September 16, 2023 @11:02AM (#63853316)
    The antivaxers will be queuing up for these, whether they have the target diseases or not.
    • Comment removed based on user account deletion

    • Re: (Score:2)

      by Z80a ( 971949 )

      If it was something you have to buy and it's a bit hard to obtain they would get it and inject on themselves no problems.
      99% of their cause is just "it's being enforced so it must be bad".

    • The antivaxers will be queuing up for these, whether they have the target diseases or not.

      There are actually a wide number of fairly readily available alternatives that naturally eliminate the body’s tolerance for learned immunities. A healthy enough dose of ricin, dihydrogen monoxide, iocaine powder, or even cyanide can do the trick, for instance, guaranteeing that your body won’t respond to any of those diseases, at which point they can’t harm you.

  • Don't take the vaccine, take the anti-vaccine. That cures everything including AIDS.

    • The A in AIDS is for "acquired", not "auto". "Acquired Immune Deficiency Syndrome" is caused by a virus so it has nothing to do with this research.

      • It was a joke, but technically if you can tell the immune system to ignore one thing, you could tell it to ignore others. Hard to reproduce if the cells don't injest.

  • Shame (Score:3)

    by SuperDre ( 982372 ) on Saturday September 16, 2023 @12:34PM (#63853500) Homepage
    It's a shame this is gonna cost so much more when it is released than the actual cost of research and production costs combined. We really should de-privatize pharmaceutical research so all medical treatments can be done at cost, which would make healthcare trillions of dollars cheaper and everybody able to get the same treatment instead of only people who can afford it (which are becoming less and less people).

    • So how do you fund the research that go nowhere?

      I mean even in all public model, "at cost" just isn't a thing here. I'm extremely pro for reigning in the ridiculous amounts of money pharma makes off not treating everyone, but this post is fundamentally misunderstanding how it would work.

    • Re: (Score:2)

      by RobinH ( 124750 )
      It literally didn't exist until someone invented it. Are you actually happier if nobody is helped than if only some people are helped?
      • I think everybody should have access to it, not only people who have the money for it, so in that regard, yes I'd rather have nobody if not everybody. But most medicine are really inflated, and the price should be limited to costprice + max 10% profit, not like what happened, some hospital pharmacy created their own pills for less then $10 a pill, but a pharmaceutical company bought the rights and sold it for $1000 a pill, even the crew of the hospital did not see that coming, as they thought the company co

  • Start human trials (Score:3)

    by Pinky's Brain ( 1158667 ) on Saturday September 16, 2023 @01:08PM (#63853560)

    MS sufferers are chemically gouging out their bone marrow now, if they can pay for it, this can hardly be much more risky.

  • If we're to assume Epstein Barr virus is a cause, this should somehow fit into that model. One possibility is viral proteins mimic natural body signaling proteins, and the immune system starts responding to both the viral mimic and natural versions. For example the EBV protein LMP1 is a viral mimic of the natural protein CD40 https://www.jbc.org/article/S0... [jbc.org]

    The PQQAT motif is bound in the same binding crevice on TRAF3 where CD40 is bound, providing a molecular mechanism for LMP1 to act as a CD40 decoy for TRAF3. The LMP1 motif is presented in the TRAF3 crevice as a close structural mimic of the PVQET motif in CD40, and the intermolecular contacts are similar. However, the viral protein makes a unique contact: a hydrogen bond network formed between Asp210 in LMP1 and Tyr395 and Arg393 in TRAF3. This intermolecular contact is not made in the CD40-TRAF3 complex. The additional hydrogen bonds may stabilize the complex and strengthen the binding to permit LMP1 to compete with CD40 for binding to the TRAF3 crevice, influencing downstream signaling to B lymphocytes and contributing to dysregulated signaling by LMP1.

    Reducing 'friendly fire' would seemingly help with things like loss of feeling etc, but I don't see how it solves the root cause. Its been shown EBV i

    • It's not about solving the root cause, it's about allowing the patient to live a symptom-free live for enough years that they die a natural death from something else. That's good enough.

  • One Dairy Anti-Vax, please (Score:3)

    by bill_mcgonigle ( 4333 ) * on Saturday September 16, 2023 @09:01PM (#63854218) Homepage Journal

    I was doing hardcore keto with almost a pound of sharp cheddar a day, while dropping a hundred pounds, when I foolishly got an immune adjuvant squirted into my deltoid one November.

    Within a month my gut would bleed from any dairy.

    No bueno. Repair molecules would be great!

  • Um, wouldn't a treatment that completely reverses a disease entirely just be a "cure", regardless of its underlying actions? What's with the new terminology?

  • Hallelujah! Any hope for us coeliac's? My immune system needs a kick in the pants and learn to tolerate gluten again (late onset coeliac at 58 years old). I would love a doughnut or a crusty French loaf in my future ....

  • ...some virus will get it's hands on pGal and attach to it? Will it mean that immune system will ignore it?

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