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.
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.
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
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.
> 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.
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.
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.
I have met enough covid antivaxers to know it would be extremely difficult to convince a huge portion of the population to take this. It would take a massive deadly virus worse and more visible than covid ever was like bleeding eyeballs in the streets before people would take this vaccination en mass
Speculative. A possible alternative approach is to not mock and antagonize them at massive scale but rather listen to their concerns, and address them non-rhetorically.
"But they threw the first punch" is a rather reasonable response, but unfortunately we have to play the hand we've been dealt, not the one we'd like to have been dealt.
Did you know, anti-vaxxers are not the only humans who are not perfectly rational? Try to imagine a scenario where it is you on the other side of the rationality table, but cannot realize it (as is the case with anti-vaxx/etc buffoons).
Everyone is doing their best, but hardly anyone is trying their hardest.
I will be the first to criticize the Canadian government and how they handled the COVID vaccine. They assured people would question it and doubt it. I won’t get into all the details as to why that is old news now but I truly think how they handled it was a failure on massive scale bordering incompetence and negligence. I did get vaccinated myself with the mandatory shots required for my job but have since not gotten any booster shots. I totally understand the side of the antivaxers but also think many of them are based on false information and propaganda some people are pushing and I have a hard time not judging those particular antivaxers.
If you think they mishandled covid, you'll love how they're handling immigration and housing!
> I totally understand the side of the antivaxers but also think many of them are based on false information and propaganda some people are pushing and I have a hard time not judging those particular antivaxers.
This is largely a consequence of them being humans raised in Western culture in the year 2024 - everyone is this way, through the degree and ways in which vary, in ways that are mostly only believed to be known - as the saying goes: a fox cannot smell his own den.
I have met enough covid vaccine injured and damaged people to come to the same conclusion. Whether perceived or actually injured. I add damaged, because those I know with heart issues, aren't ever going to be fully recovered.
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:
> 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.
mRNA vaccines aren't really modifying genes or changing expression in the way CRISPR or RNAi can.
Given the reaction to even the most basic deployment of a new technique, I doubt there will be mass adoption of more complex technique that alter gene expression any time soon.
However, these tools are too powerful to ignore. The most likely outcome is that these tools will be approved to cure rare diseases (CRISPR is already approved for sickle cell for example). A few decades of use will help ease anxiety about their use and safety.
My point is that someone that is strongly pro-vaccine is more harmful than not. I'd rather have someone that is just going to be unbiased and stick the scientific method. When you are doing something risky, the risk averse opinion, even if misguided, is far more safe than the the person who's vision is clouded by their preferences.
of additional note, 2 FDA officials resigned during the votes on approving booster shots. They were simply replaced, and their concerns were moot. They were hardly anti-vaxxers.
> someone that is strongly pro-vaccine is more harmful than not.
You make it sound like " someone that is strongly pro-vaccine" is like the supporter of a football team or a "my country right or wrong" person, and therefor "harmful", rather than someone who has reached a decision based on weight of evidence.
And I do not see that as accurate at all. In fact it is harmful.
The original commenter made to comparison of anti-vaxxer vs strongly pro-vaccine, to me, that kind of comparison elicits both extremes of the spectrum.
But putting that aside, since I don't think it's a productive discussion- I'm simply pro zero bias. The only bias that should exist is a bias towards non-intervention over interventions. This used to be the standard for evaluating any medicine or vaccine. Or any medical procedure in general.
The real important bias issue that I see with the FDA doesn't have so much to do with vaccines specifically, but more with the incestuous relationship between FDA and Pharmaceutical companies, with there being a revolving door of blurry incentives. There's a long running issue of FDA officials, after approving various drugs and treatments for big pharma...then promoting into a big fat salary with a pharmaceutical company. I'm not sure what the solution is, as it makes logical sense that someone at the FDA would share the same skillsets as a big pharma exec, but- the only solution I can think of is to ensure that there are always skeptics on approval boards.
Looking at this from outside the USA, the emphasis that you place on the USA's FDA in calling the shots seems parochial and misplaced. And a bit conspiratorial.
I do not take your claim of "zero bias" seriously while you make comments about "covid vaccine injured and damaged people" - sic.
I do not take your claims about "bias towards non-intervention" seriously when you cannot mention the far higher incidence of heart issues etc that results from deliberate withholding of vaccinations.
> ensure that there are always skeptics on approval boards.
I think that the issue is still that there is more than one definition of "skeptics" and as said above, the anti-vaxxer ideologues simply do not think things through well enough to be of any benefit. See your non-serious claims above.
I'm glad you're able to handily dismiss my arguments, because my lived experiences are non-serious. My formerly very active friends in their late twenties/early thirties that developed POTS after vaccination, not after contracting covid, they simply did not think things through enough to make the right conclusions about their experiences.
It's hard to confirm they didn't contract covid or one of the other similar things that popped up during the "tripledemic" after the lockdown started to lift, especially since it sounds like a cluster of people that might have caught something strange from each other and that also report a rare side effect.
FWIW, I had some issues that showed up after getting not-covid. They seem to have gone away after a few months of cardio workouts; hope your friends recover.
All instances of POTS showed up across friends with no overlap, on different ends of the country. The several people that came down with bells palsy- also not in overlapping groups. The latter is associated with the covid shots, the former, not as much, as it's also suspected to occur after covid infection as well, though it's hard to trust the statistics. My friends that suspected the vaccine as the culprit were very aggressively dismissed by their doctors, so I doubt many of those reports were ever logged.
I'm glad you recovered, and thanks for the well wishes.
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)
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
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.
> 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.
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
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]
Still not seeing that claim, I'm still reading though, but so far it seems to actually claim the opposite. Some of the failings of MRNAI is that it's temporary.
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
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.
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.
> 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.
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.
"But they threw the first punch" is a rather reasonable response, but unfortunately we have to play the hand we've been dealt, not the one we'd like to have been dealt.
Did you know, anti-vaxxers are not the only humans who are not perfectly rational? Try to imagine a scenario where it is you on the other side of the rationality table, but cannot realize it (as is the case with anti-vaxx/etc buffoons).
Everyone is doing their best, but hardly anyone is trying their hardest.
> I totally understand the side of the antivaxers but also think many of them are based on false information and propaganda some people are pushing and I have a hard time not judging those particular antivaxers.
This is largely a consequence of them being humans raised in Western culture in the year 2024 - everyone is this way, through the degree and ways in which vary, in ways that are mostly only believed to be known - as the saying goes: a fox cannot smell his own den.
> 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.
Given the reaction to even the most basic deployment of a new technique, I doubt there will be mass adoption of more complex technique that alter gene expression any time soon.
However, these tools are too powerful to ignore. The most likely outcome is that these tools will be approved to cure rare diseases (CRISPR is already approved for sickle cell for example). A few decades of use will help ease anxiety about their use and safety.
The latter group is more likely to be involved in vaccine approval processes.
I'd rather have skeptics involved in high risk approvals.
of additional note, 2 FDA officials resigned during the votes on approving booster shots. They were simply replaced, and their concerns were moot. They were hardly anti-vaxxers.
You make it sound like " someone that is strongly pro-vaccine" is like the supporter of a football team or a "my country right or wrong" person, and therefor "harmful", rather than someone who has reached a decision based on weight of evidence.
And I do not see that as accurate at all. In fact it is harmful.
But putting that aside, since I don't think it's a productive discussion- I'm simply pro zero bias. The only bias that should exist is a bias towards non-intervention over interventions. This used to be the standard for evaluating any medicine or vaccine. Or any medical procedure in general.
The real important bias issue that I see with the FDA doesn't have so much to do with vaccines specifically, but more with the incestuous relationship between FDA and Pharmaceutical companies, with there being a revolving door of blurry incentives. There's a long running issue of FDA officials, after approving various drugs and treatments for big pharma...then promoting into a big fat salary with a pharmaceutical company. I'm not sure what the solution is, as it makes logical sense that someone at the FDA would share the same skillsets as a big pharma exec, but- the only solution I can think of is to ensure that there are always skeptics on approval boards.
There are no sides or spectrum to this, vaccines are one of the most life saving inventions in human history. To be pro-vaccine means being rational.
> I'm simply pro zero bias
There’s no such thing.
I do not take your claim of "zero bias" seriously while you make comments about "covid vaccine injured and damaged people" - sic.
I do not take your claims about "bias towards non-intervention" seriously when you cannot mention the far higher incidence of heart issues etc that results from deliberate withholding of vaccinations.
> ensure that there are always skeptics on approval boards.
I think that the issue is still that there is more than one definition of "skeptics" and as said above, the anti-vaxxer ideologues simply do not think things through well enough to be of any benefit. See your non-serious claims above.
FWIW, I had some issues that showed up after getting not-covid. They seem to have gone away after a few months of cardio workouts; hope your friends recover.
I'm glad you recovered, and thanks for the well wishes.
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.
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.
https://www.pnas.org/doi/10.1073/pnas.2317274121
Why can't we just add this to the headline always ..
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/emerge...
2. https://www.statnews.com/2024/02/01/updated-covid-vaccine-ef...
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314794/
4. https://vaccineknowledge.ox.ac.uk/mmr-vaccine#:~:text=The%20....
5. https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/about-vacc...
6. https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html
7. https://shingrixhcp.com/efficacy-safety/efficacy-data/
EDITED: added extra citation on RNAi.
9. https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=C....
https://www.synthego.com/blog/rnai-vs-crispr-guide#:~:text=C....