Could Recreating a Rare Mutation Grant Almost Universal Virus Immunity For Days? (columbia.edu)
- Reference: 0178852204
- News link: https://science.slashdot.org/story/25/08/25/0242216/could-recreating-a-rare-mutation-grant-almost-universal-virus-immunity-for-days
- Source link: https://www.cuimc.columbia.edu/news/one-universal-antiviral-rule-them-all
> 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.
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> 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...
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> 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...."
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> "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 [2]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."
[3]More coverage from ScienceAlert .
[1] https://www.cuimc.columbia.edu/news/one-universal-antiviral-rule-them-all
[2] https://www.cuimc.columbia.edu/news/one-universal-antiviral-rule-them-all
[3] https://www.sciencealert.com/recreating-a-rare-mutation-could-grant-almost-universal-virus-immunity-for-days
Rare side effects inheretent to mRNA platform (Score:1)
While this discovery appears to have promise, mRNA delivery platform has known and unsolved issues. Namely, it is not currently possible to control what cells absorb encoded nanoparticles, this in turn leads to uncontrolled cell death. Most of the time, it is muscle tissue around injection site, but there are circumstances when these circulate and end up in highly detrimental places, like the heart tissue. Consequently, effectiveness of such potential treatment should be balanced against potential side effe
Batsur (Score:3)
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: [1]https://www.science.org/doi/10... [science.org]
[1] https://www.science.org/doi/10.1126/scitranslmed.adx5758
RFK will kill this in (Score:3)
3...2...1...
I'm really hoping Betteridge's law ... (Score:1)
... of headlines is wrong here.
Re: (Score:2)
If such powerful ability existed in nature, these mutations would have long since spread through population even if highly detrimental otherwise. 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. TFA discusses something much more powerful and broadly effective.
Re: (Score:2)
> 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 [1]severe ulcerations in the neck and armpits don't restrict their reproductive chances, those in the groin probably would. [frontiersin.org].
(Image from [2]This paper. [frontiersin.org])
[1] https://www.frontiersin.org/files/Articles/1287258/fimmu-14-1287258-HTML/image_m/fimmu-14-1287258-g001.jpg
[2] https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1287258/full