Could Recreating a Rare Mutation Grant Almost Universal Virus Immunity For Days? (columbia.edu) 55
"For a few dozen people in the world, the downside of living with a rare immune condition comes with a surprising superpower — the ability to fight off all viruses..." notes an announcement from Columbia University.
"At first, the condition only seemed to increase vulnerability to some bacterial infections. But as more patients were identified, its unexpected antiviral benefits became apparent."
Columbia immunologist Dusan Bogunovic discovered the individuals' antiviral powers about 15 years ago, soon after he identified the genetic mutation that causes the condition... Bogunovic, a professor of pediatric immunology at Columbia University's Vagelos College of Physicians and Surgeons, soon learned that everyone with the mutation, which causes a deficiency in an immune regulator called ISG15, has mild, but persistent systemic inflammation... "In the back of my mind, I kept thinking that if we could produce this type of light immune activation in other people, we could protect them from just about any virus," Bogunovic says.
Today, Bogunovic is closing in on a therapeutic strategy that could provide that broad-spectrum protection against viruses and become an important weapon in next pandemic. In his latest study, published August 13 in Science Translational Medicine, Bogunovic and his team report that an experimental therapy they've developed temporarily gives recipients (hamsters and mice, so far) the same antiviral superpower as people with ISG15 deficiency. When administered prophylactically into the animals' lungs via a nasal drip, the therapy prevented viral replication of influenza and SARS-CoV-2 viruses and lessened disease severity. In cell culture, "we have yet to find a virus that can break through the therapy's defenses," Bogunovic says...
Bogunovic's therapeutic turns on production of 10 proteins that are primarily responsible for the broad antiviral protection. The current design resembles COVID mRNA vaccines but with a twist: Ten mRNAs encoding the 10 proteins are packaged inside a lipid nanoparticle. Once the nanoparticles are absorbed by the recipient's cells, the cells generate the ten host proteins to produce the antiviral protection. "We only generate a small amount of these ten proteins, for a very short time, and that leads to much less inflammation than what we see in ISG15-deficient individuals," Bogunovic says. "But that inflammation is enough to prevent antiviral diseases...."
"We believe the technology will work even if we don't know the identity of the virus," Bogunovic says. Importantly, the antiviral protection provided by the technology will not prevent people from developing their own immunological memory to the virus for longer-term protection.
"Our findings reinforce the power of research driven by curiosity without preconceived notions," Bogunovic says in the announcement. "We were not looking for an antiviral when we began studying our rare patients, but the studies have inspired the potential development of a universal antiviral for everyone."
More coverage from ScienceAlert.
Today, Bogunovic is closing in on a therapeutic strategy that could provide that broad-spectrum protection against viruses and become an important weapon in next pandemic. In his latest study, published August 13 in Science Translational Medicine, Bogunovic and his team report that an experimental therapy they've developed temporarily gives recipients (hamsters and mice, so far) the same antiviral superpower as people with ISG15 deficiency. When administered prophylactically into the animals' lungs via a nasal drip, the therapy prevented viral replication of influenza and SARS-CoV-2 viruses and lessened disease severity. In cell culture, "we have yet to find a virus that can break through the therapy's defenses," Bogunovic says...
Bogunovic's therapeutic turns on production of 10 proteins that are primarily responsible for the broad antiviral protection. The current design resembles COVID mRNA vaccines but with a twist: Ten mRNAs encoding the 10 proteins are packaged inside a lipid nanoparticle. Once the nanoparticles are absorbed by the recipient's cells, the cells generate the ten host proteins to produce the antiviral protection. "We only generate a small amount of these ten proteins, for a very short time, and that leads to much less inflammation than what we see in ISG15-deficient individuals," Bogunovic says. "But that inflammation is enough to prevent antiviral diseases...."
"We believe the technology will work even if we don't know the identity of the virus," Bogunovic says. Importantly, the antiviral protection provided by the technology will not prevent people from developing their own immunological memory to the virus for longer-term protection.
"Our findings reinforce the power of research driven by curiosity without preconceived notions," Bogunovic says in the announcement. "We were not looking for an antiviral when we began studying our rare patients, but the studies have inspired the potential development of a universal antiviral for everyone."
More coverage from ScienceAlert.
I'm really hoping Betteridge's law ... (Score:1)
... of headlines is wrong here.
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Re:I'm really hoping Betteridge's law ... (Score:5, Interesting)
If such powerful ability existed in nature, these mutations would have long since spread through population even if highly detrimental otherwise.
I suspect this one would be too detrimental.
Even if someone with ISG15 deficiency would survive the necrosis long enough to hit puberty in a pre-modern medicine environment, then if the severe ulcerations in the neck and armpits don't restrict their reproductive chances, those in the groin probably would. [frontiersin.org].
(Image from This paper. [frontiersin.org])
Re:I'm really hoping Betteridge's law ... (Score:5, Informative)
For example, Sickle Cell Disease is highly debilitating but prevalent in some populations due to immunity to malaria. This is just one disease and Sickle Cell can kill you.
You're missing a very important part of this. Sickle Cell Disease is when you inherit the mutation from both parents, and it's generally fatal. When you inherit the mutation from only one parent, you don't get Sickle Cell Disease, but it still affects the red blood cells enough that you get significant resistance to malaria. So the mutation stays in the population because getting it from one parent is highly beneficial, even though getting it from both parents is highly deleterious.
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Bacterial infections are generally worse than viral infections, so I don't think that argument holds. You can find specific exceptions, but it's not the general rule. Also keeping inflammation high has lots of other risks, like increasing the danger of anaphylactic shock, and using more energy. It would probably also increase the rate of aging, but that's more of a guess.
Doing it "for days" might well be safe, and worth the cost in some circumstances, though.
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Note the 'for days'. This doesn't sound too promising.
Sounds like they would achieve this by making people 'pre-sick' by having their immune system in a sustained inflammatory state, for a while. This points to both an inability to keep it going, and likely not a very pleasant experience for the relatively short while it is effective. You'd have to know within a few days when you are *going* to get exposed to a virus..
Practically speaking, any pandemic will be bouncing around long enough for this likely
The "for days" is the important part (Score:1)
I wouldn't want to be in a constant state of inflammation, but if I were a health-care worker getting a shot every few days for a period of a few weeks during an acute epidemic/pandemic would be very useful.
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I suppose if you *know* you will get exposed, then you could have a window where you could be in a state of inflammation, get infected, and come out the other side with a durable immune response and discontinue.
Problem being that if you don't know when you'll have been infected, hard to say when it stops. As we saw with COVID-19, it can be a *long* time of active pandemic to try to get through. I guess if this, hypothetically, worked as promised you get to get treated, then have something like a 'COVID pa
Ebola Re:The "for days" is the important part (Score:2)
If I were a health-care worker in an area where Ebola outbreaks happened from time to time, I would want this "4-day vaccine" available. As soon as anyone in my community had a suspected case, I'd take the shot and keep taking it until all local cases were over with.
I'd still do all of the standard Ebola-prevention and -mitigation strategies. This would be just one more layer.
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Other than a "COVID party" you could potentially use something like this (all assuming that it actually works, of course) for just a regular party or other social event. Let's say you isolate for weeks at a time, then have a super social weekend where you go to multiple parties or places with large crowds, etc. and you dose up specifically for that weekend (whether or not you would also take antibiotics as a prophylactic measure is in question), then discontinue after.
Of course, this plan depends on some un
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Imagine this. You are a health care worker. You find out that the patient that came in this morning had Ebola and you were definitely exposed.
That patient is dead now. Do you want the shot?
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It's a nice dream, right?
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Namely, it is not currently possible to control what cells absorb encoded nanoparticles
When I got the mRNA covid vaccine, and subsequent boosters, they controlled the cells that absorbed the encoded nanoparticles to mostly muscle cells in my left shoulder, by injecting them into the muscle of my left shoulder.
this in turn leads to uncontrolled cell death.
ISG15 deficiency often presents with uncontrolled cell death ... better known as necrosis. The therapy seems to be very self-limiting.
But can you point me to a source discussing uncontrolled cell death as a consequence of using mRNA as a delivery platform? My google-fu is failing me.
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Are you a molecular biologist or something?
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Something
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No references, so I doubt you known shit about what you are whining about. On the other hand, there are the over 1 million Americans who croaked because of Covid, the mRNA vaccine protected millions from suffering the same fate.
Which Witch Doctor do you use?
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Biodistribution of RNA Vaccines and of Their Products: Evidence from H [mdpi.com]
Batsur (Score:5, Interesting)
I still think we should be looking very close at Bats for how to build the ultimate response to viruses. Bats are not immune to viruses, but they just dont seem to be hurt by them, almost *any* virus. As best we can tell this has to do with a lack of inflamatory response. Likely an evolutionary compromise where evolution said "Ok, we wont stop viruses, but we will stop reacting to them", as a sickly bat is a bat thats unable to survive. Now, I suspect that just doing that to humans wont be very useful, as we actually do need that strong response to viruses as unlike bats, humans have a long lifespan, and that gives viruses the ability to do real long term harm to the genome, cancer and all that. But combining a strong antiviral therapy with something that reduces or eliminates inflamation might at least make certain nastier viruses a lot more survivable.
Though this does seem at odds with the approach in the paper.
FYI, the actual paper is here: https://www.science.org/doi/10... [science.org]
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I still think we should be looking very close at Bats for how to build the ultimate response to viruses. Bats are not immune to viruses, but they just don't seem to be hurt by them, almost *any* virus. As best we can tell this has to do with a lack of inflammatory response. Likely an evolutionary compromise where evolution said "Ok, we wont stop viruses, but we will stop reacting to them", as a sickly bat is a bat thats unable to survive. Now, I suspect that just doing that to humans wont be very useful, as we actually do need that strong response to viruses as
Not disagreeing with you, but I seem to remember a paper once that talked about the fact that the human immune system appears to "over react" to many benign things and that this immune behavior may have been due to some evolutionary event in our history. One of the disadvantages of this strong response appears to be things like allergies that suddenly crop up for no apparent reason.
Crocodiles and Giant Indonesian lizards (Score:2)
RFK will kill this in (Score:5, Insightful)
3...2...1...
Re:RFK will kill this in (Score:5, Funny)
I am waiting for him to show up in a White House press conference with a bone through his nose and a shaking rattle at all the evil spirits in the conference room.
RFK, jr.: Begone, foul beasts of Beelzebub!!
Beelzebub explodes up through the floor boards, shaking his tail, gouging marks in the gold leafed ceiling with his horns, eyes glowing.
Beelz: You rang?
RFK, jr.: Bbbllllbblllll.....I didn't think you were real.
Beelz: Of course I'm real, got your soul in this jar already (rattles jar with what appears to be BB in it).
"I want some hot stuff baby this evening, I want some hot stuff baby tonight"....Beelz's iPhone rings....Beelz picks up.
God: Hey Beelz, how are they hanging?
Beelz: Like two over-excited gondolas in a hurricane. Hi there, Big Guy, what can I do you for?
God: Stop pestering that yokel. You've already got his soul.
Beelz: Errrrmmm, let me take another chunk out of him, just a little one.
God: NO! Look at his face, one more chunk and he'll go tits up....and you know what that means!!
Beelz, now seeing the danger: Ah, Mr. JFK jr,, just keep on what you are doing, I love more dead people.
JFK, jr.: To what was God referring?
Beelz: Nothing, nothing, think no more about it. I try not to.
JFK, jr. confers with aide and looks up aghast: Mr. Beelz, I am not fit for Down There.
Beelz: Ya, I know, but I'll find a place for you with the Prosperity Preachers. Here, try this rattle, its mo' better than yours.
Beelz pulls out magic wand and disapparates back to Down There....the dulcet tones of AC/DC thunder around the conference room...."I'm on the Highway to Hell...."
JFK, jr., now all excited and shaking his new rattle.
St. Peter dials Beelz, "I want some hot stuff baby this evening, I want some hot stuff baby tonight"....Beelz's iPhone rings....Beelz picks up.
St. Pete: Hi there, Beelz, how are they hanging?
Beelz: Like two high school girls excited about the Prom, they can skip rope now. What can I do you for?
St. Pete: What was in that rattle you gave RFK., jr.?
Beelz: The souls of la Presidenta's cabinet.
St. Pete: You Devil!! Every time he shakes it, 10 more Americans die.
Beelz: I like to think of it as new Full Employment Policy. Their alleged administration seems to like it.
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3...2...1...
I love how ignorance loves to imply that RFK is the "killer" these days. As opposed to sugar, HFCS, caffeine, nicotine, alcohol, and every other poison that was once touted as beneficial for your health. Remember when doctors were sponsoring cigarettes? History does.
Grow the fuck up and pull your head out of Politiks ass already. RFK is not your enemy. Your ignorance is.
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Our ignorance is the problem and not RFK's? Really? Look I know there's a subtle distinction between actively killing people and simply sabotaging efforts to save people, but still, cancelling research into things like lifesaving cancer therapies for children is kind of close enough.
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Not just that, but RFK is directly responsible for bunch of children dying needlessly in Samoa. The blood is figuratively directly on his hands. Now he's trying to do that to children in the US. The one good thing he's promoting does not excuse the bazillion horrible things he's doing, especially since the dismantling of the regulatory apparatus by the administration [gutting of the DoA, FDA, etc.] would take the teeth out of any positive food health initiatives RFK might be promoting. I can unequivocal
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Let's just get everyone's immune system riled up for the next disease that's roughly as deadly as the flu. That's a great idea.
Feel free to protect your immune system from having to do any work. Hopefully you don't also think a a lack of exercise is good for your muscles, heart, or brain.
I wonder if it will work in humans for rabies (Score:4, Insightful)
Right now, the survival rate for symptomatic rabies is near zero.
So, if you could take a shot that nukes every virus in your body for a few days, and thereby rid yourself of rabies... that would be worth putting up with a few days of elevated inflammation. It might suck, but there's a pretty good chance that it would suck a lot less than dying of rabies.
Re:I wonder if it will work in humans for rabies (Score:5, Funny)
Right now, the survival rate for symptomatic rabies is near zero.
So, if you could take a shot that nukes every virus in your body for a few days, and thereby rid yourself of rabies... that would be worth putting up with a few days of elevated inflammation. It might suck, but there's a pretty good chance that it would suck a lot less than dying of rabies.
This concept should get RFK foaming at the mouth.
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I see what you did there, and I appreciate it.
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Right now, the survival rate for symptomatic rabies is near zero.
So, if you could take a shot that nukes every virus in your body for a few days, and thereby rid yourself of rabies... that would be worth putting up with a few days of elevated inflammation. It might suck, but there's a pretty good chance that it would suck a lot less than dying of rabies.
This concept should get RFK foaming at the mouth.
Even if you are doing the whole "RFK vaccine nyuk nyuk" bit, something that you just take a few days because you contracted a disease doesn't sound like it fits that whole thing?
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While being anti-vaccine is certainly a big part of RFK jr's schtick, there's plenty of other nutso anti-science, anti-medicine stuff rattling around in there. Now, in true stopped clock fashion, there are some things in there that are practical health advice, exercise, avoid over-processed foods, excessive sugar, food dyes, etc. Of course, that's just the usual common sense, back of the (ironically full of sugar, salt, food dyes, etc.) cereal box stuff. Just because no one sane would disagree with it does
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There's too much around for the existing therapies to work, obviously... But are there any existing therapies that work like this one? I don't see how we could know until we try.
And yeah, vaccination is a much better idea. But by the time you know you should have gotten one, it's too late.
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I mean, you don't need to take it before interacting with animals. If there's that much of a concern, it's not like there isn't a vaccine already that you should take instead. Taking it once bitten is a possibility, but there's already a treatment to take when you're bitten and suspect possible rabies as well. So the only hope of this helping as opposed to existing therapies (although maybe this works better? Unknown) is if it can actually help once you are symptomatic.
As I understand it, the actual mechani
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If you stopped all inflammatory response somehow, then you'd die of necrosis as the infected cells broke down and you either got secondary bacterial infection or just kinda fell apart radiation sickness style.
Eventually. The question is still how long dying from the consequences of stopping inflammatory response would take compared to how long it takes a disease that normally kills you from your own inflammatory response to stop being an issue. Inflammation is not the only immune response your body has against viruses, plus there are other medical anti-viral treatments. There are also antibiotics for bacterial infections, etc. So it might be a question of stopping inflammatory response long enough that the viral
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And that is different (at the level of analogy) to treatments like chemotherapy how? I will note that firefighting does cause damage like you describe, but firefighters still fight fires, amazingly enough. The same applies to medical treatment, given an option between an invariably fatal illness and a dangerous treatment, the frequent medical choice is the dangerous treatment. The very specific example was rabies, which is at least higher than 99.9% fatal in humans. We are not talking about permanently endi
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No, the inflammatory response /is/ the immune response, the chemokines used to communicate and coordinate cell behavior cause immune recruitment to where it is needed, and this requires increased blood flow, which results in inflammation.
Ah, I see the confusion. I did mention that I did not know a lot about the inflammatory response, but it appears that what I do know about it is more than you. The inflammatory response is not _the_ immune response, it is _an_ immune response. Part of the whole, but not the whole. Something that accelerates and aids the response and is, in itself part of the response, but is still just one part. There are plenty of parts of the immune system that still operate independently of the inflammatory response. Tha
I'm not a doctor but I know this isn't a thing: (Score:1)
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Well, poisoning technically counts as a disease and most antivirals are poisonous, so maybe they mean antiviral overdoses? Or maybe just internal use of bleach? Anal fistula caused by UV lightbulb insertion? Severe radiation poisoning might directly destroy viruses or at least prevent viral replication (lethal radiation poisoning will definitely prevent viral replication).
I guess it could just be a typo though, but that's less fun.
Getting closer, Trump cuts funding.... (Score:5, Informative)
ALL? Really? (Score:2)
Have they actually exposed these mutated people to *all* viruses, proving that they are immune to all of them? Viruses are a whole spectrum of pathogens, many of which haven't even been discovered yet, or don't even exist yet. New ones are evolving all the time.
When the first COVID vaccines came out, some of them were *highly* effective, preventing illness as much as 90% of the time. But guess what, the virus evolved, and continues to evolve. Why would we think this new mutation would escape evolutionary ad