5 ms·

Vaccine strategy that is effective against any strain of a virus in mice

67 points by gmays 3y ago

ceejayoz 3y ago
Link to the paper, unfortunately, goes to a 404.
- egberts1 3y ago
  https://www.pnas.org/doi/10.1073/pnas.2317274121 https://www.pnas.org/doi/10.1073/pnas.2317274121
  - fsiefken 3y ago
    That's the wrong paper, it mentions mice and rna, but no mention of vaccines or viruses, only bacteria. The authors are not from UC Riverside but from Scandinavia. It was received October 11, 2023; accepted March 12, 2024
tombert 3y ago
I don't know anything about biology; how clickbaitey is the headline for this? It sounds awesome, but I always take "breakthrough" medical news with a huge grain of salt.
- searine 3y ago
  The special sauce here is that they are using "RNAi", or RNA interference to reduce expression of viral proteins. This is a very well vetted technique in a research setting, but is not a clinical tool. There has been a tremendous hesitancy to using more advanced gene editing and expression modifying techniques in a clinical setting. People just don't like it. So, yes, this would likely work, but it would be very difficult to bring to market for human use.
  - rob74 3y ago
    Yeah, the mRNA vaccines that appeared during the last years were also only made possible after some very significant issues were ironed out. To quote from https://en.wikipedia.org/wiki/Katalin_Karik%C3%B3 https://en.wikipedia.org/wiki/Katalin_Karik%C3%B3: > Before 2005, a major problem with the proposed therapeutic use of mRNA was that in vivo use led to inflammatory reactions. A key insight came about when Karikó focused on why transfer RNA (tRNA), used as a control in an experiment, did not provoke the same immune reaction as mRNA. [...] Karikó and Weissman determined how specific nucleoside modifications in mRNA led to a reduced immune response: by replacing uridine with pseudouridine. > Another important achievement by the researchers was the development of a delivery technique to package the mRNA in lipid nanoparticles, a novel pharmaceutical drug delivery system for mRNA. The mRNA is injected into tiny fat droplets (lipid nanoparticles) which protect the fragile molecule until it can reach the desired area of the body.
  - UberFly 3y ago
    Didn't Covid vaccines kinda kick down the door though? Might be less hesitancy because of that.
    - incrudible 3y ago
      To the contrary, people are more skeptical of vaccines than ever, leading to a drop even in proven childhood vaccinations.
      - hedora 3y ago
        There are more anti-vaxxers, but also more people that are strongly pro-vaccine. The latter group is more likely to be involved in vaccine approval processes.
        deleted 3y ago
        [deleted]
        yonaguska 3y ago
        > The latter group is more likely to be involved in vaccine approval processes. I'd rather have skeptics involved in high risk approvals.
- NortySpock 3y ago
  Well, the next step would be safety tests -- verifying that the shot doesn't give the recipient an auto-immune disease, where the body is taught to attack a part of itself.
  - mistermann 3y ago
    [flagged]
- jewayne 3y ago
  The subheading is either deeply ignorant or actively misleading -- "End of the line for endless boosters?". No, it's not the end of the line for endless boosters. Humans do not retain lifetime immunity to many kinds of viruses -- the flu among them. Even if we do develop a universal flu vaccine, you will still need a periodic booster. The main difference will be that it could be the same exact vaccine, year after year. And yes, you might not need it every single year, either. But you almost certainly would still need boosters.
  - DangitBobby 3y ago
    I'm guessing the headline came from this snippet: > When the researchers tested this strategy with a mouse virus called Nodamura, they did it with mutant mice lacking T and B cells. With one vaccine injection, they found the mice were protected from a lethal dose of the unmodified virus for at least 90 days. Note that some studies show nine mouse days are roughly equivalent to one human year. So assuming you can extrapolate to human timescales, it would be booster every 10 years. I also doubt it will be effective that long. Would have been nice for them to mention how long normal vaccines remain effective in mice.
    - thrtythreeforty 3y ago
      To me, the headline makes too strong of a claim to be backed up by such a weak statement - "some studies," "roughly equivalent," etc. Some studies show lots of things which you'd do well not to base any actions on.
- hammock 3y ago
  Well, it's in mice first of all. And it has nothing to do with the mRNA vaccines that are popular right now. Here's how it works in layman's terms: The "vaccine" is really a dose of a mutant virus that is the same as the virus you are supposedly infected with, with one key difference: this mutant virus is unable to fight off your body's immune system. But, like the original virus, it still triggers your immune system (to make RNAi). So, the vaccine (the mutant virus), replicates in your body and infects you, as the original virus is infecting you. Your immune system responds (the RNAi), doubly so, since it is seeing not only the original virus but also the mutant virus, and this double-size (not really double but the idea is..."more", "stronger") immune response is enough to knock out the original virus
  - RetroTechie 3y ago
    > Well, it's in mice first of all. And it has nothing to do with the mRNA vaccines that are popular right now. So it's a novel strategy for vaccines. And it seems to be working. That combo should qualify as "breakthrough" I think? Sure, it may fail later on in clinical trials. But potentially a huge step forward.
cycomanic 3y ago
How is it possible that they messed the link to the paper up in their press release?!
- tambourine_man 3y ago
  Yeah, that’s pretty bad. Some really bold claims that require a lot of substance. It would be awesome, though.
- cycomanic 3y ago
  Replying to myself. There's no recent article by the lead author on PNAS, I think they fired the gun to early and the article has actually not been published yet (still under embargo likely)
BizarroLand 3y ago
I wonder how broad this could actually go? Does this mean that we could have an HIV vaccine within our lifetimes?
- unsupp0rted 3y ago
  Or a Herpes vaccine- HIV is far, far less prevalent than Herpes is. And it's probably easier to avoid getting HIV than it is to avoid getting Herpes.
  - BizarroLand 3y ago
    I've heard that by the time you die, 7/10 people have it. Could be big money for the developer.
- SideburnsOfDoom 3y ago
  There is progress on HIV. I don't think that it's related to this though: https://www.independent.co.uk/news/health/hiv-cure-cell-test-dna-b2515169.html https://www.independent.co.uk/news/health/hiv-cure-cell-test...
Quarrel 3y ago
In mice. Why can't we just add this to the headline always ..
- OJFord 3y ago
  > Loading a trillion rows of weather data into TimescaleDB in mice
  - layer8 3y ago
    You’re misunderstanding. It would be “Loading a trillion rows of weather data into mice“.
  - sieste 3y ago
    seems like a simple browser extension
- layer8 3y ago
  Maybe add to the headline when it’s not in mice, much less work.
deleted 3y ago
[deleted]
COGlory 3y ago
Ah the hubris. I can't check the original paper because the DOI is missing (and I don't have time to go searching). But my takeaway is they are avoiding protein targeting altogether. Typical vaccines for something like SARS will target the SARS spike protein which looks a bit like a rose on a stem. The stem is the part that sits in the body of the SARS itself, while the rose petals are the bit that your immune system actually can see. As a result, the rose petals mutate quite frequently, meaning that your immune system is constantly chasing a moving target. Whereas the stem can't mutate nearly as easily without breaking and making the virus ineffective. This is a common viral strategy. Viruses coat the parts that they can't mutate due to their structure-function importance with parts they can mutate easily because they are mostly just decoration. That way, your immune system only sees the easily changed decoration. Rather than target the proteins with antibodies, they are not worry about the virus entering the cell, and are instead targeting the viral genomes by making complementary RNA molecules (i.e. the inverse of the viruses ssRNA genome). This means that when the virus unwraps its genome in your cell, this vaccine will immediately bind to the genome and prevent it from being read/replicated. This isn't completely novel, your body already does this naturally, but viruses typically have pieces that will prevent your body's natural response from working. They must have found a way around that. Also, they must have solved the delivery mechanism somehow? RNA is notoriously unstable and doesn't usually make a suitable vaccine for that reason, although recent mRNA vaccines have also solved this problem I guess. It's not clear if it's an mRNA vaccine that produces the iRNA, or if they're delivering the iRNA directly.
- Izkata 3y ago
  > Also, they must have solved the delivery mechanism somehow? RNA is notoriously unstable and doesn't usually make a suitable vaccine for that reason, although recent mRNA vaccines have also solved this problem I guess. No, they rely on the instability to clear it out of your system so you're not creating spike proteins indefinitely. It's supposed to be temporary because the long-lasting part is what your body's immune system learns over that relatively short duration.
- egberts1 3y ago
  The PNAS paper link to the PDF document. https://www.pnas.org/doi/10.1073/pnas.2317274121 https://www.pnas.org/doi/10.1073/pnas.2317274121
Fire-Dragon-DoL 3y ago
I'm hopeful, I'm tired of being poked twice per year (covid, influenza)
egberts1 3y ago
Edited for extra citations Only downside is that RNAi (and mRNA) are uncorrectable once introduced.[9] I fear for the brave volunteers of such a drug trial, or worse those manufacturers who skip the FDA trial through Emergency Use Authorization. [1] ICYMI: The COVID19 inoculant efficacy rating is 54% [2] and still falling, yet still remains unapproved by FDA. Most pediatric and adult vaccines boast 85+%.[4][5][6][7] Of course, not everyone understands what efficacy rate is. [3] 1. https://www.fda.gov/vaccines-blood-biologics/vaccines/emergency-use-authorization-vaccines-explained https://www.fda.gov/vaccines-blood-biologics/vaccines/emerge... 2. https://www.statnews.com/2024/02/01/updated-covid-vaccine-effectiveness/ https://www.statnews.com/2024/02/01/updated-covid-vaccine-ef... 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314794/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314794/ 4. https://vaccineknowledge.ox.ac.uk/mmr-vaccine#:~:text=The%20vaccine%20works%20very%20well,some%20point%2C%20usually%20as%20children https://vaccineknowledge.ox.ac.uk/mmr-vaccine#:~:text=The%20.... 5. https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/about-vaccine.html#:~:text=In%20studies%20demonstrating%20the%20efficacy,the%20last%20dose%20of%20DTaP https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/about-vacc... 6. https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html 7. https://shingrixhcp.com/efficacy-safety/efficacy-data/ https://shingrixhcp.com/efficacy-safety/efficacy-data/ EDITED: added extra citation on RNAi. 9. https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=Comparing%20Specificity%20of%20CRISPR%20and,for%20gene%20function%20screening%20experiments https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=C....
- tshannon 3y ago
  Is there a reference for this claim? "Only downside is that RNAi (and mRNA) are uncorrectable once introduced."
  - egberts1 3y ago
    thanks, added it above and here. https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=Comparing%20Specificity%20of%20CRISPR%20and,for%20gene%20function%20screening%20experiments https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=C....

67 points by gmays 3y ago

ceejayoz 3y ago

Link to the paper, unfortunately, goes to a 404.

egberts1 3y ago
https://www.pnas.org/doi/10.1073/pnas.2317274121 https://www.pnas.org/doi/10.1073/pnas.2317274121
- fsiefken 3y ago
  That's the wrong paper, it mentions mice and rna, but no mention of vaccines or viruses, only bacteria. The authors are not from UC Riverside but from Scandinavia. It was received October 11, 2023; accepted March 12, 2024

tombert 3y ago

I don't know anything about biology; how clickbaitey is the headline for this? It sounds awesome, but I always take "breakthrough" medical news with a huge grain of salt.

searine 3y ago
The special sauce here is that they are using "RNAi", or RNA interference to reduce expression of viral proteins. This is a very well vetted technique in a research setting, but is not a clinical tool. There has been a tremendous hesitancy to using more advanced gene editing and expression modifying techniques in a clinical setting. People just don't like it. So, yes, this would likely work, but it would be very difficult to bring to market for human use.
- rob74 3y ago
  Yeah, the mRNA vaccines that appeared during the last years were also only made possible after some very significant issues were ironed out. To quote from https://en.wikipedia.org/wiki/Katalin_Karik%C3%B3 https://en.wikipedia.org/wiki/Katalin_Karik%C3%B3: > Before 2005, a major problem with the proposed therapeutic use of mRNA was that in vivo use led to inflammatory reactions. A key insight came about when Karikó focused on why transfer RNA (tRNA), used as a control in an experiment, did not provoke the same immune reaction as mRNA. [...] Karikó and Weissman determined how specific nucleoside modifications in mRNA led to a reduced immune response: by replacing uridine with pseudouridine. > Another important achievement by the researchers was the development of a delivery technique to package the mRNA in lipid nanoparticles, a novel pharmaceutical drug delivery system for mRNA. The mRNA is injected into tiny fat droplets (lipid nanoparticles) which protect the fragile molecule until it can reach the desired area of the body.
- UberFly 3y ago
  Didn't Covid vaccines kinda kick down the door though? Might be less hesitancy because of that.
  - incrudible 3y ago
    To the contrary, people are more skeptical of vaccines than ever, leading to a drop even in proven childhood vaccinations.
    - hedora 3y ago
      There are more anti-vaxxers, but also more people that are strongly pro-vaccine. The latter group is more likely to be involved in vaccine approval processes.
      - deleted 3y ago
        [deleted]
      - yonaguska 3y ago
        > The latter group is more likely to be involved in vaccine approval processes. I'd rather have skeptics involved in high risk approvals.
NortySpock 3y ago
Well, the next step would be safety tests -- verifying that the shot doesn't give the recipient an auto-immune disease, where the body is taught to attack a part of itself.
- mistermann 3y ago
  [flagged]
jewayne 3y ago
The subheading is either deeply ignorant or actively misleading -- "End of the line for endless boosters?". No, it's not the end of the line for endless boosters. Humans do not retain lifetime immunity to many kinds of viruses -- the flu among them. Even if we do develop a universal flu vaccine, you will still need a periodic booster. The main difference will be that it could be the same exact vaccine, year after year. And yes, you might not need it every single year, either. But you almost certainly would still need boosters.
- DangitBobby 3y ago
  I'm guessing the headline came from this snippet: > When the researchers tested this strategy with a mouse virus called Nodamura, they did it with mutant mice lacking T and B cells. With one vaccine injection, they found the mice were protected from a lethal dose of the unmodified virus for at least 90 days. Note that some studies show nine mouse days are roughly equivalent to one human year. So assuming you can extrapolate to human timescales, it would be booster every 10 years. I also doubt it will be effective that long. Would have been nice for them to mention how long normal vaccines remain effective in mice.
  - thrtythreeforty 3y ago
    To me, the headline makes too strong of a claim to be backed up by such a weak statement - "some studies," "roughly equivalent," etc. Some studies show lots of things which you'd do well not to base any actions on.
hammock 3y ago
Well, it's in mice first of all. And it has nothing to do with the mRNA vaccines that are popular right now. Here's how it works in layman's terms: The "vaccine" is really a dose of a mutant virus that is the same as the virus you are supposedly infected with, with one key difference: this mutant virus is unable to fight off your body's immune system. But, like the original virus, it still triggers your immune system (to make RNAi). So, the vaccine (the mutant virus), replicates in your body and infects you, as the original virus is infecting you. Your immune system responds (the RNAi), doubly so, since it is seeing not only the original virus but also the mutant virus, and this double-size (not really double but the idea is..."more", "stronger") immune response is enough to knock out the original virus
- RetroTechie 3y ago
  > Well, it's in mice first of all. And it has nothing to do with the mRNA vaccines that are popular right now. So it's a novel strategy for vaccines. And it seems to be working. That combo should qualify as "breakthrough" I think? Sure, it may fail later on in clinical trials. But potentially a huge step forward.

cycomanic 3y ago

How is it possible that they messed the link to the paper up in their press release?!

tambourine_man 3y ago
Yeah, that’s pretty bad. Some really bold claims that require a lot of substance. It would be awesome, though.
cycomanic 3y ago
Replying to myself. There's no recent article by the lead author on PNAS, I think they fired the gun to early and the article has actually not been published yet (still under embargo likely)

BizarroLand 3y ago

I wonder how broad this could actually go? Does this mean that we could have an HIV vaccine within our lifetimes?

unsupp0rted 3y ago
Or a Herpes vaccine- HIV is far, far less prevalent than Herpes is. And it's probably easier to avoid getting HIV than it is to avoid getting Herpes.
- BizarroLand 3y ago
  I've heard that by the time you die, 7/10 people have it. Could be big money for the developer.
SideburnsOfDoom 3y ago
There is progress on HIV. I don't think that it's related to this though: https://www.independent.co.uk/news/health/hiv-cure-cell-test-dna-b2515169.html https://www.independent.co.uk/news/health/hiv-cure-cell-test...

Quarrel 3y ago

In mice. Why can't we just add this to the headline always ..

OJFord 3y ago
> Loading a trillion rows of weather data into TimescaleDB in mice
- layer8 3y ago
  You’re misunderstanding. It would be “Loading a trillion rows of weather data into mice“.
- sieste 3y ago
  seems like a simple browser extension
layer8 3y ago
Maybe add to the headline when it’s not in mice, much less work.

deleted 3y ago

[deleted]

COGlory 3y ago

Ah the hubris. I can't check the original paper because the DOI is missing (and I don't have time to go searching). But my takeaway is they are avoiding protein targeting altogether. Typical vaccines for something like SARS will target the SARS spike protein which looks a bit like a rose on a stem. The stem is the part that sits in the body of the SARS itself, while the rose petals are the bit that your immune system actually can see. As a result, the rose petals mutate quite frequently, meaning that your immune system is constantly chasing a moving target. Whereas the stem can't mutate nearly as easily without breaking and making the virus ineffective. This is a common viral strategy. Viruses coat the parts that they can't mutate due to their structure-function importance with parts they can mutate easily because they are mostly just decoration. That way, your immune system only sees the easily changed decoration. Rather than target the proteins with antibodies, they are not worry about the virus entering the cell, and are instead targeting the viral genomes by making complementary RNA molecules (i.e. the inverse of the viruses ssRNA genome). This means that when the virus unwraps its genome in your cell, this vaccine will immediately bind to the genome and prevent it from being read/replicated. This isn't completely novel, your body already does this naturally, but viruses typically have pieces that will prevent your body's natural response from working. They must have found a way around that. Also, they must have solved the delivery mechanism somehow? RNA is notoriously unstable and doesn't usually make a suitable vaccine for that reason, although recent mRNA vaccines have also solved this problem I guess. It's not clear if it's an mRNA vaccine that produces the iRNA, or if they're delivering the iRNA directly.

Izkata 3y ago
> Also, they must have solved the delivery mechanism somehow? RNA is notoriously unstable and doesn't usually make a suitable vaccine for that reason, although recent mRNA vaccines have also solved this problem I guess. No, they rely on the instability to clear it out of your system so you're not creating spike proteins indefinitely. It's supposed to be temporary because the long-lasting part is what your body's immune system learns over that relatively short duration.
egberts1 3y ago
The PNAS paper link to the PDF document. https://www.pnas.org/doi/10.1073/pnas.2317274121 https://www.pnas.org/doi/10.1073/pnas.2317274121

Fire-Dragon-DoL 3y ago

I'm hopeful, I'm tired of being poked twice per year (covid, influenza)

egberts1 3y ago

Edited for extra citations Only downside is that RNAi (and mRNA) are uncorrectable once introduced.[9] I fear for the brave volunteers of such a drug trial, or worse those manufacturers who skip the FDA trial through Emergency Use Authorization. [1] ICYMI: The COVID19 inoculant efficacy rating is 54% [2] and still falling, yet still remains unapproved by FDA. Most pediatric and adult vaccines boast 85+%.[4][5][6][7] Of course, not everyone understands what efficacy rate is. [3] 1. https://www.fda.gov/vaccines-blood-biologics/vaccines/emergency-use-authorization-vaccines-explained https://www.fda.gov/vaccines-blood-biologics/vaccines/emerge... 2. https://www.statnews.com/2024/02/01/updated-covid-vaccine-effectiveness/ https://www.statnews.com/2024/02/01/updated-covid-vaccine-ef... 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314794/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314794/ 4. https://vaccineknowledge.ox.ac.uk/mmr-vaccine#:~:text=The%20vaccine%20works%20very%20well,some%20point%2C%20usually%20as%20children https://vaccineknowledge.ox.ac.uk/mmr-vaccine#:~:text=The%20.... 5. https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/about-vaccine.html#:~:text=In%20studies%20demonstrating%20the%20efficacy,the%20last%20dose%20of%20DTaP https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/about-vacc... 6. https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html 7. https://shingrixhcp.com/efficacy-safety/efficacy-data/ https://shingrixhcp.com/efficacy-safety/efficacy-data/ EDITED: added extra citation on RNAi. 9. https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=Comparing%20Specificity%20of%20CRISPR%20and,for%20gene%20function%20screening%20experiments https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=C....

tshannon 3y ago
Is there a reference for this claim? "Only downside is that RNAi (and mRNA) are uncorrectable once introduced."
- egberts1 3y ago
  thanks, added it above and here. https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=Comparing%20Specificity%20of%20CRISPR%20and,for%20gene%20function%20screening%20experiments https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=C....