“Inverse vaccine” shows potential to treat MS and other autoimmune diseases | Hacker News Reader

“Inverse vaccine” shows potential to treat MS and other autoimmune diseases

pme.uchicago.edu

254 pointsmanicennui98 comments

"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 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

New bioweapon just dropped

Because creating a substance that when injected selectively turns off immune response to a single molecule is going to be way easier to administer, cheaper to manufacture, and more effective than say airborn anthrax spores...

Did any person in the world send the container of the mandatory vaccine to a lab to find out what they were actually administered?

Wingnuts that think there's a vaccine conspiracy come from all walks of life, but they all share a complete lack of understanding of any aspect of the pharmaceutical industry. If that's the world you want to believe in I strongly encourage you to opt out of all forms of healthcare.

Which vaccine are you referring to? Any distributed vaccine in the US has a rigorous chain of custody, if tampering is what you're worried about.

Can anyone weigh in with information as to how insulated this is from being overbearing and giving someone some form of immune deficiency syndrome?

I'm personally skeptical of the entire concept of autoimmune disease. I think something else is going on -- something other than the immune system losing its mind and attacking healthy tissue for no real reason.

If autoimmune disease is a flawed concept, then treating it this way could potentially go very bad places.

That’s a pretty fringe belief from my (limited!) understanding of the human immune system.

Why do you think that?

I have a genetic disorder. I've seen lots of weird ideas about what the body is supposedly doing that simply don't make sense.

You can have people with Psoriatic Arthritis creating legions on their skin. You give them an immune suppressant and the legions go away. Please explain to me your alternative hypothesis for this mode of action.

Our immune system is dysfunctioning because of something (not natural occurrence)

What is that something? - vaccines - toxins, pesticides? - lack of vitamin D, infrared? Something else?

Our modern medicine (pharma companies) are succeeding at making us chronically sick as that is what is more lucrative, it’s literally the matrix, we are serving the machine, not the other way around.

Whatever is causing immune problems is at the same time creating a lot of shareholder value.

But we spot these diseases the world over, not just in the US where it is lucrative.

A lot of countries this medication is purchased and bargained for at the government level and then provided to individuals for low cost/no cost (outside of tax).

It’s also assessed at the total population level. So I don’t know how you could convince a country (say) to buy something that makes them ill then sell them the cure. They have the efficacy data of both things.

Or are you suggesting that it is a cross industry collision, like shampoo that create diabetes, and then they sell us diabetes cures?

> Our immune system is dysfunctioning because of something (not natural occurrence)

So, an autoimmune disease? Because that falls within the parameters of what you've described.

> What is that something? - vaccines - toxins, pesticides? - lack of vitamin D, infrared? Something else?

The question of why autoimmune diseases are becoming more common is good one. There is research that shows correlations between the incidence of autoimmune disease and vitamin D deficiency and exposure to microplastics. But as of now, these are just correlations. Causality has not been established, and there are a lot of missing links left on that road.

> Whatever is causing immune problems is at the same time creating a lot of shareholder value.

You give way too much credit to big pharma.

1. We don't know enough about autoimmune disease to know how to intentionally cause it.

2. As with many conspiracy theories, this one relies on the very improbable occurrence of tens of thousands of people keeping mum over multiple decades and not a single one of them growing a conscience at any point. Or just leaking something out of incompetence at any point.

You are right, It think it’s mostly caused by the change of our environment: screens, less time outside, food getting industrialized, etc.

On the side of pharma it’s mostly: work on what is lucrative, don’t kill the golden goose (fix the problem)

They have a huge incentives to keep the problems going and create a subscription model to alleviate the symptoms, not surprising, that exactly what they do.

If inverse vaccines work, they will end the most lucrative drugs in the history of medicine.

Humira the OG biologic treatment for autoimmune conditions costs $5,000/month. There has been a gold rush by pharmaceutical companies to create humira-like drugs or new monoclonal antibodies. Enbrel, Simponi, Taltz, Rinvoq and on. They all cost thousands of dollars per month and must be taken for life.

Immune suppresant biologics has been one of the biggest profit growth areas for pharma over the last 20 years. They are all chasing it. These inverse vaccines would end that.

You don't need to know how to intentionally cause it to come up with solutions that help keep it alive. All you need is a profit motive that helps keep your eye on profiting from ongoing treatment and helps you parrot the party line that "It's incurable."

See also The Shirky Principle: Organizations tend to keep alive the problem they are intended to address.

This article is literally about a permeant or semi-permenant cure for diseases which are currently treated with drugs costing as much as tens of thousands of dollars per month. The profit motive would be not to bring inverse vaccines to market.

That doesn't somehow rebut my point. No industry is ever a monolith.

No industry is a monolith, and yet there's not a single whistleblower that's come forward? There's not a single hedge fund that's dropped a Hindenburg style expose as it short sells a pharma company's stock?

This is a really interesting question. There is the issue that Pfizer is too big to fail and there is no situation where countries that bet their democratic legitimacy on Pfizer products are going to prosecute them, so there isn't a short case you can publish and reasonably time. The thing about betting on conspiracy theories is that the theories only exist because they're getting away with it. They say you should buy the rumor and sell the news, but the smarter play may be to buy the conspiracy theory - and then just hold indefinitely.

Currently on the front page of HN:

California sues 5 major oil co's for campaign of deception about climate change

https://news.ycombinator.com/item?id=37540420

And it's hardly the first time that it came to light industry insiders knew X caused harm and suppressed it for decades.

What makes that a not-analogous example is that there is an active campaign to destroy oil companies, most likely as a means to nationalize them as there is no situation in the next 100 years where oil goes away, and also that this is California where nothing is real.

Vitamin D deficiency is linked to autoimmune disorders, but through a larger mechanism. As I (a layman, not a doctor) understand it, the autoimmune disorder phenomenon is now thought to be the result of two things:

a) DNA from viral infections in previous generations (HERV, Human Endogenous Retro-Viruses), and

b) infection with a similar virus.

The HERV gives autoimmune diseases a genetic component, which is why not everyone gets them, and the infection with a similar virus (like Epstein-Barr for multiple sclerosis) triggers the body to start attacking itself because it finds the HERV. Vitamin D can help suppress the expression of HERV, so vitamin D deficiency can contribute to the problem—but it's not the root of the problem.

https://www.imrpress.com/journal/JIN/20/1/10.31083/j.jin.202...

So you have listed three potential explanations:

1. Vitamin D deficiency.

2. Genetic disorder

3. Viral infection

All of which are specific causes that are potentially treatable and do not fit with "the immune system has lost its mind and is randomly attacking healthy tissue."

Let me try to fill in. Prior infection with something can leave behind genetic changes (which can also be passed to offspring, even across many generations). The changes may or may not cause a disorder. Subsequent infection by a similar agent may cause the immune system to "learn" aspects of that agent. This can then cause the immune system to identify similar aspects of host cells, and mount a response to the perceived threat.

Relatedly, allergies are also a class of immune disorder based on misidentification. For instance, toxicodendron plants like "poison ivy" produce a harmless substance that is capable of chemically bonding to human cell membranes, which does not seem to impair the primary function of the cell, but does alter its ability to respond correctly when "interrogated" by relevant T-cells. These T-cells are immune cells which can be described as drifting through the body, randomly attaching to other cells, and then asking those cells to authenticate. The response from an affected cell is malformed, causing the T-cell to release a chemical signal which is like say "Kill everything here!". This causes other immune cells which enter the area to commence destroying friend and foe alike. More immune cells will continue to be recruited for as long as the 'kill' signal lasts. The signal will continue to be produced each time another cell fails to authenticate.

Thank you.

Failure to authenticate does not sound to me like "the immune system loses its mind and randomly attacks healthy tissue." It sounds more like "sometimes something messes up a normal security check and this results in security personnel being called in droves."

Kind of like SWATting.

Why is the person who treats most autoimmune diseases called a rheumatologist? Because the people who documented and categorized these diseases in Western medicine were believers in Humorism. That is a belief that human ailments stem from the imbalance of the four humors (blood, green bile, black bile and phlegm). They believed the inflammation in these disorders was the product of a phlegm imbalance, specifically of the mucus rheum. Hence the field name of Rheumatology.

The name dates back to the 17th century. My history is a little shaky, but as far as I can recall, the 17th century was before pharmaceuticals, pesticides and the entire industrial revolution. But maybe I need to get on that Gary Kasperov history where the Roman Empire fell in like 1940 or whatever.

I suspect you meant lesions rather than legions?

Yes, Swype keyboard fail.

> If autoimmune disease is a flawed concept

Then testing this technology might prove your hypothesis.

Perhaps.

Except a lot of studies are poorly done, humans are prone to confirmation bias, "serious" medical experiments can be awful stuff of a sort that won't get approved -- and rightly so.

Trying to get buy-in on new ideas can be shockingly hard.

Autoimmune is studied and understood deeply enough to be believable.

Tell me you don’t know anyone with an autoimmune disease without telling me.

Go talk to people with autoimmune diseases and then report back. There’s a good chance you’ll end up deleting your comment

If you take a biopsy of an inflamed part of the intestine in a person with ulcerative colitis, you can stain the cells in that sample, look at them under a microscope, and see a lot of gunk collecting around the nucleus that you don't see in the same type of cell in a healthy person. (This gunk is called p-ANCA, if you're interested in looking it up.)

If you take that gunk and analyze it with x-ray crystallography, you find that the compound in this gunk has the structure of an antibody.

I'd love to hear the intersection of Occam's razor and how you explain these findings with a theory other than autoimmune disease.

Well, considering that current treatments for these diseases involve a broad based suppression of the immune system which lead to substantial increases risk from routine infection, they would have to be pretty bad to do worse than the current standard of care.

For example, the near state-of-the-art in immune suppression is the IL-17 inhibitor. IL-17 itself is a crucial signaller for Cytokine production. And it signals a broad array of Citokines. Citokines are essential in fighting most forms of infection. So, to have side effects as bad as a modern immune suppressant, an "inverse vaccine" would have to have a generalized effect as bad as global Citokine suppression. That would be an extraordinary leap for a drug which is meant to tell T cells to ignore one specific molecule.

This is using the body’s own mechanism to develop tolerance to an antigen that is recognized as “self”. Nothing would stop the body from developing an immune response at a later time.

If there's such an easy biological mechanism to indicate "this one is fine", then I'm surprised it isn't being exploited by infectious agents already.

Imagine a virus that causes cells to also produce proteins that tell the immune system the virus is a friend.

I seem to recall that this is a known "side effect" of measles where it removes many immunities if you catch it.

Here's a 2019 article, "Study suggests how measles depletes body’s immune memory"[0] which (despite the title) seems to quantify the percentage of antibody arsenal that is lost after a measles infection. Sadly, I haven't had luck finding resources to answer "by what mechanism does measles cause antibody memory to be lost?", but I've got a good thing to ponder for the weekend. Thanks. :)

[0] https://news.harvard.edu/gazette/story/2019/10/how-measles-w...

Also, HIV depletes your T cells

And SARS-CoV-2, unfortunately.

?? 99.9% of people recover just fine and surely they still have their T cells

It’s probably a waste of breath on this forum at this point, but look it up, and how long it takes even HIV infected individuals to become clinically immunodeficient.

How confident are you in your position? Literally 30 seconds spent searching: https://www.nature.com/articles/s41418-022-00936-x

I've only skimmed it, but doesn't the article you linked indicate that it is only true for severe/ life-threatening cases of COVID-19?

Doesn't matter, it shows that covid can deplete t-cells as claimed up-thread.

extreme cases of covid is not relevant for 99.9% of people so that's sufficiently close enough to say your claim is exaggerated. Sure, colds can kill too, but we don't treat them the same as Ebola.

The claim that a thing happens is not invalidated by it's relative frequency. You don't get to pretend lightning doesn't exist despite the relative rarity of people being hit by it.

Here you go: https://asm.org/Articles/2019/May/Measles-and-Immune-Amnesia

Very short version: it infects the tissue that create the cells that contain or immune memory, replacing them with versions that only know about the measles virus. Sounds like it's not permanent, though the article doesn't make it clear whether it's recovery or re-learning.

Our immune system is quite aggressive with garbage collection and can picky about what pathogens it chooses to remember. This behaviour makes sense on the hypothesis that our immune system has a "storage limit" for immunities. It doesn't make sense if the immunity memory is unlimited.

(The reason why many vaccines require boosters is that without the repeat exposure, our immune system decides it doesn't need to remember about that particular pathogen.)

There are many such signals and they are already being exploited by pathogens. Such things are also exploited by tumors. That's why figuring out hard basic immunology problems like transplantation (while managing associated infections) will probably generate knowledge that is likely to help cure cancer, and vice versa. A lot of the time glycans (sugars) are a key part of what makes something look like self vs non-self.

Regulatory T cells and infection: a dangerous necessity https://www.nature.com/articles/nri2189

Sialic acid utilization by bacterial pathogens https://www.microbiologyresearch.org/content/journal/micro/1...

Hallmarks of glycosylation in cancer https://www.oncotarget.com/article/8155/text/

Trypanosomas change their protein markers to hide from the immune system. My recollection is this is why you can't create a vaccine for them.

There already are diseases that hide from the immune system, things like hepatitis B, herpes, shingles.

It’s nothing new.

Could we vaccinate Herpes to forget how to latch on to cells?

Not really.

The current approach is to try and find an antigen on the herpes virus that the virus can't stop the immune system from recognizing.

Or use antivirals to stop the reproduction process, and the virus eventually dies. That's the approach with hepatitis C.

No. If you create a strain of a disease that is less persistent, it would obviously be wiped out almost instantly by basic natural selection.

Some gut parasites release immunosuppressants to protect themselves , it's also actively being traild on humans who suffer from autoimmune gut diseases

I hope this will be useful in treating food allergies. It also seems to be potentially scary to be attempting inverse vaccines while our understanding of the mechanics of immunity are so limited.

Looks like the same team is already looking into treating food allergies with inverse vaccine https://foodallergyfund.org/research-1/2021/2/15/inverse-foo....

Wow. This is a big deal: autoimmune diseases are one of the hardest to treat.

The same strategy presumably could be applied for something like Crohn's disease. And I guess at a long shot, might work if IBS has an autoimmune component.

Wonder if it could treat arthritis? It like another commenter said, allergies.

Another article on this mentioned both as possible uses for this. They called out rheumatoid arthritis in particular. There's lots of diseases with autoimmune components, that this could be a game changer for. I'm cautiously optimistic.

I remember reading discussions about mRNA vaccines being created to sensitize against immune system molecules, like in the way that Dupixent is just a monoclonal antibody that works against certain interleukins. So many interesting things out there for people with autoimmune diseases!

Wow, if this is real and practical it could be huge! Right up there with sanitation, nutrition, antibiotics and vaccines.

Anyone have context as to how the name came to be? When I think of inverse vaccine, I think of something that gives you a disease. This is suggestive of erasing memory instead.

Super exciting work nonetheless.

Because immune tolerance is the opposite of immune protection, when it comes to the adaptive immune system, whose business is deciding what to do the next time it encounters an antigen (it's a memory response either way).

But really what they found here should maybe be called an inverse vaccine adjuvant (the part of the vaccine which tells your immune system that the associated antigen is dangerous, and a protective response should be mounted to it)

Vaccines activate the immune system. Inverse vaccine suppress it.

When anti-antivaccine demonstrations? In all seriousness, fantastic news.

There is no cure for autoimmune diseases atm, although some promising research in disease modifying drugs like https://www.kennedy.ox.ac.uk/news/new-drug-offers-hope-for-p...

This sounds like a far more targeted approach that could work for most autoimmune diseases (maybe even allergies?)

As an owner of a rare "MS-like disease" aka MOGAD I cant wait. The point of this treatment is that if you know which protein is the trigger you can stop it. It's probably not a cure, but an even better alternative to the current treatments that all cause at least some side effects or are not entirely effective.

I should note that I know of active phase 2 trials by other campanies for type 1 diabetes.

> I should note that I know of active phase 2 trials by other campanies for type 1 diabetes

For those less informed and unfortunate owners of this malice, can you elaborate?

Yeah, sorry, was on my phone.

I've been following this company: http://imcyse.com/pipeline#type-1-diabetes

First, disclaimer, I'm a patient (MOGAD), not a medical professional. As far as phases goes, as far as I understand it, phase 1 is safety, phase 2 is initial trial for efficacy.

Quote from the website about Type 1 diabetes:

> In Type 1 diabetes (T1D), the insulin-producing beta cells in the pancreas are destroyed through an autoimmune attack. The loss of beta cells leads to insulin insufficiency and hyperglycemia, with patients eventually requiring lifelong insulin therapy to maintain normal glycemic control.

...

>IMCY-0098, a synthetic peptide based on insulin (one of the proteins to which the body begins to mount an aberrant immune response) is designed to halt the progression of diabetes by stopping the body’s immune system from attacking beta cells. With early intervention, the pancreas’ ability to produce insulin may be preserved, enabling patients to manage the disease with minimal insulin injections and hopefully in some cases without the need for insulin at all.

> In a Phase 1b study with 41 newly diagnosed patients, IMCY-0098, was found to be safe and well tolerated, with steady levels of C-peptides detected in some T1D patients up to 6 months following treatment, providing an encouraging signal for the Imotope™ platform.

> IMCY-0098 is currently being investigated in a Phase 2 multicenter, randomized, double-blind, placebo-controlled, dose comparison study in patients with recent onset T1D. .... The study completed recruitment in March 2023 exceeding its recruitment target, with a total of 110 patients enrolled and randomized across 28 clinical sites in Europe, the United States and Australia. Efficacy proof-of-concept data from IMPACT is expected in Q1 2024.

Another application: erasing original antigenic sin.

I wonder if this could be used to address allergies as well.

Isn't this already how we address allergies?

Allergy shots include the small amounts of the allergen, given in such doses as to allow the immune system to build a tolerance to the allergen. [0][1] It reminds me of psychology's "exposure therapy". [2] In layman's terms, allergy shots teach the immune system to chill, whereas this "inverse vaccine" (as I understand it) deletes a substance from the immune system's memory.

[0] https://www.mayoclinic.org/tests-procedures/allergy-shots/ab...

[1] https://my.clevelandclinic.org/health/treatments/25194-aller...

[2] https://en.wikipedia.org/wiki/Exposure_therapy

I think the commenter was referring to immunosuppressive therapy.

Yes, the approach in the article is very similar. The difference is that the antigen is tagged with molecules that heighten the recognition of the antigen as “self”.

So same concept, just an improved approach.

In less layman's terms from someone that is still a layman - isn't it less akin to exposure therapy and more that it modulates the immune response from one type to another (IgE to IgG4), the second response being less associated with the traditional symptoms of allergies but for which we are not entirely sure what the full impacts are? In other words the body still responds abnormally but with a different mechanism. Furthermore we aren't entirely sure why high levels of exposure shift the response from one IG to another?

Oh! I honestly have no idea because that isn't something I noticed in my admittedly shallow research. But you've given me some great questions to ask my allergist next week. Thanks!

I can see how this works for slow autoimmune diseases mentioned in the article. But I suppose using it for fast autoimmune diseases is more difficult (thinking about Guillaume Barré Syndrome in particular, which can get you to an IC in 48 hours).

I can already hear keyboards clacking away of fiction authors writing books of intrigue about this technology coming to fruition. Russia weaponizes it by creating a virus that has been engineered to emit variations of this knock-out molecule, making the recipient able to get sick again from a host of common illnesses. All Russian citizens have been given immunity from this new virus before it is unleashed on the world. Within weeks, nobody is immune from measles, chicken pox, mumps, etc. A huge wave of sickness envelops the world, giving Russia the upper hand as the militia of all its enemies are desperately ill.

> The new “inverse vaccine” does just the opposite: it removes the immune system’s memory of one molecule

Very cool, but what would happen if that molecule was small pox?

Since smallpox was eradicated over 40 years ago and most people alive today have not been vaccinated against it, I doubt it would matter much.

Smallpox is one heist away from being unleashed on the world again, if that. And with most people unvaccinated, well... there's your bioweapon.

Then you don't need to remove any immunity, right?

The US and Europe haven't vaccinated for smallpox since the early '70s and routine vaccination wrapped up globally in the mid-'80s, so, for many... absolutely nothing.

I used to be amused when period pieces would show actresses (particularly European) in sleeveless attire with their smallpox vaccine scar, three feet tall in the closeup shots.

Turns out smallpox vaccines are a lot older than I thought. They might have not looked exactly like that in Victorian England, but an iteration of it did already exist. Guess that's why they cover up tattoos but not smallpox scars.

I know many people in my country, Spain, who are 60+ and have smallpox vaccine scars.

Yeah the movies I'm thinking of, those people would be 40-60 today, maybe a little bit older.

I used to have a smallpox scar but it eventually faded away. I am in my 50s.

Yeah the first effective Smallpox vaccines were almost 230 years ago, and actually predates the Victorian era by a couple of decades.

Vaccination through exposing healthy people to smallpox to build immunity goes back to like 200 BCE. [1]

[1] https://www.who.int/news-room/spotlight/history-of-vaccinati...

Good question!

s/small pox/a marker for a harmful agent/

smallpox is a bit more than a molecule.

More generally, if you told the immune system to ignore a still existing disease, it would probably be defenseless if/when you actually got infected by it.

Or could the immune system maybe override this if you got really sick?

Add I understand it, it's not about actively ignoring something. Rather, the immune system somehow learned to react more strongly to specific antigens, and undoing that. The natural immune reaction should still happen when encountering diseases, and not when encountering normal body tissues.

It's possible to use such tricks to actively shut down the immune system, but you either have to incorporate it into the disease (which actually happens in nature) or take that medicine continuously.

Now, is this going to be "safe and effective", and kill and mame people, or actually work?

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