Moderna will develop mRNA vaccines for some of the world’s worst diseases(singularityhub.com)
singularityhub.com
Moderna will develop mRNA vaccines for some of the world’s worst diseases
https://singularityhub.com/2022/03/10/moderna-to-develop-mrna-vaccines-for-15-diseases-that-threaten-global-health/
184 comments
Original press release from Moderna: https://investors.modernatx.com/news/news-details/2022/Moder...
The targeted diseases are: Chikungunya virus, COVID-19, Crimean-Congo haemorrhagic fever, Dengue, Ebola virus disease, HIV, Malaria, Marburg virus disease, Lassa fever, Middle East respiratory syndrome coronavirus (MERS-CoV), Nipah and henipaviral diseases, Rift Valley fever, Severe fever with Thrombocytopenia syndrome, Tuberculosis, Zika
Dengue is a disease that vaccination actually makes worse, at least with the ones we have now. I'm wondering how they sidestep those issues.
There were early vaccines for SARS in the early 2000s that also made it worse if you actually caught SARS. I dont think this is a disease specific property, hopefully the Moderna approach will work as it does with COVID.
A statement like this one requires a proper reference. Otherwise looks like anti vaccine ad.
Man, I hate the way that anything about vaccine side effects gets flanderized into "ANTIVAXXERS!". However I hate the "educate yourself" movement more, so here I am. (I missed out the "can" though, that's on me)
First a WHO link.:
https://www.who.int/news-room/questions-and-answers/item/den...
>There is an increased risk of hospitalized and severe dengue in seronegative individuals starting about 30 months after the first dose.
TL;DR vaxx good if you've been infected before, but if you're dengue naive, it might raise the risk of severe side effects
Now, on the topic of an actual immunological phenomenon with a name out of /pol/'s fever dreams: An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014204/
TL;DR: Original antigenic sin describes a situation where the body's first exposure to an antigen shapes it's future response. This ends tragically in the case of dengue, where the response trained on a serotype is unfortunately overfit. Upon exposure to a different dengue serotype, the immune system defaults the response fit to the original infection, resulting in a response dominated by an inferior antibody. The outcomes are thus worse.
From what I'm seeing in more recent publications this model of dengue infection still seems to be the general consensus.
As to why I dug into this area in the first place, I live somewhere where dengue was quite the bugbear, and the "second time kills you" story was mentioned quite a bit. Turns out it's a pretty interesting area, since it clashes with the layman concept of immunity. I'm no expert in this domain though, so if I've missed out some progression on the science here, I'd really like to know.
Edit:
As others have also pointed out, there's also the case where the antibodies even enhance the infection process.
First a WHO link.:
https://www.who.int/news-room/questions-and-answers/item/den...
>There is an increased risk of hospitalized and severe dengue in seronegative individuals starting about 30 months after the first dose.
TL;DR vaxx good if you've been infected before, but if you're dengue naive, it might raise the risk of severe side effects
Now, on the topic of an actual immunological phenomenon with a name out of /pol/'s fever dreams: An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014204/
TL;DR: Original antigenic sin describes a situation where the body's first exposure to an antigen shapes it's future response. This ends tragically in the case of dengue, where the response trained on a serotype is unfortunately overfit. Upon exposure to a different dengue serotype, the immune system defaults the response fit to the original infection, resulting in a response dominated by an inferior antibody. The outcomes are thus worse.
From what I'm seeing in more recent publications this model of dengue infection still seems to be the general consensus.
As to why I dug into this area in the first place, I live somewhere where dengue was quite the bugbear, and the "second time kills you" story was mentioned quite a bit. Turns out it's a pretty interesting area, since it clashes with the layman concept of immunity. I'm no expert in this domain though, so if I've missed out some progression on the science here, I'd really like to know.
Edit:
As others have also pointed out, there's also the case where the antibodies even enhance the infection process.
Very simplified
Dengue has multiple strains. The initial infection with one strain tends to be not so bad and you may acquire immunity to it. However, it triggers a much worse, often hemorrhagic outcome if you acquire one of the other strains.
Vaccines, afaik mirror that property, changing the risk calculation by removing the less risky first infection.
Dengue has multiple strains. The initial infection with one strain tends to be not so bad and you may acquire immunity to it. However, it triggers a much worse, often hemorrhagic outcome if you acquire one of the other strains.
Vaccines, afaik mirror that property, changing the risk calculation by removing the less risky first infection.
It's a commonly known limitation of all Dengue vaccines. You can look it up in Wikipedia. This is also why there are no dengue vaccines widely used today.
> As Drew Weissman, one of the physician-scientists who helped develop mRNA vaccine technology put it, “mRNA vaccines are essentially plug and play. We believe you can change the part of the mRNA that encodes a protein, plugging in new code specific to the virus we hope to protect against, and cause one’s body to produce proteins that match that virus’ proteins. We do not have to develop and manufacture an entirely new formula.”
I think this quote sufficiently answers your curiosity slightly. Not a lot, but slightly.
I think this quote sufficiently answers your curiosity slightly. Not a lot, but slightly.
Unfortunately not, I'm aware of how the mrna vaccines work.
The issue with dengue in particular is a bit of a special case. Infection with a single serotype weakens the body against infection with other serotypes. Now. This poses a challenge to vaccination, as you need to find a way to get all four.
Currently, we have dengvaxia, which does do that. However, an interesting effect is that the vaccination is only useful if you already have a history of dengue. If you're dengue naive, the vaxx increases the risk of severe disease instead.
The issue with dengue in particular is a bit of a special case. Infection with a single serotype weakens the body against infection with other serotypes. Now. This poses a challenge to vaccination, as you need to find a way to get all four.
Currently, we have dengvaxia, which does do that. However, an interesting effect is that the vaccination is only useful if you already have a history of dengue. If you're dengue naive, the vaxx increases the risk of severe disease instead.
> However, an interesting effect is that the vaccination is only useful if you already have a history of dengue. If you're dengue naive, the vaxx increases the risk of severe disease instead.
I was concerned about this potentially being a thing with Covid at one point. Thankfully not the case, but yeah...
I was concerned about this potentially being a thing with Covid at one point. Thankfully not the case, but yeah...
I don’t think it does. With dengue fever the issue is once you develop antibodies the first time, the second time you get infected the antibodies actually increase the viruses chances of binding to whatever it binds to, so the effectiveness of the virus increases.
I’m not sure how mRNA vaccines get around that, but I imagine they have a plan, it would be interesting to hear it.
I’m not sure how mRNA vaccines get around that, but I imagine they have a plan, it would be interesting to hear it.
When mRNA vaccines were invented, I was told that it had the advantage that a mRNA vaccine can be easily modified so as to be effective against a mutated virus. Yet after so many mutations of covid, all we have is still the original version of covid mRNA vaccine. Why?
Updated vaccines _have_ been developed and are in trials. Moderna created a beta variant vaccine last year that is the furthest along in any trial IIRC. Pfizer has an alpha variant specific booster with quite good results from trials too.
The problem as I understand it is that it isn't profitable for either company to take a risk on producing these boosters at scale. They have to take a bet that the variant they target for the booster will be the one to dominate in the next months, and right now with variants like omicron mutating and growing at astounding rates it is quite risky. If they target the wrong variant that's a whole lot of completely wasted vaccine doses and they have to start over again. As I understand it their production lines are limited too and can only produce one specific type of vaccine or booster at once (i.e. wild type or new variant, but not both).
Honestly we need operation warp speed again. It needs to just never stop, at least while we are in such a critical stage and massive amount of virus spread. We need the government and the billionaires/trillionaires to bankroll parallel development of all major variant boosters at once.
The problem as I understand it is that it isn't profitable for either company to take a risk on producing these boosters at scale. They have to take a bet that the variant they target for the booster will be the one to dominate in the next months, and right now with variants like omicron mutating and growing at astounding rates it is quite risky. If they target the wrong variant that's a whole lot of completely wasted vaccine doses and they have to start over again. As I understand it their production lines are limited too and can only produce one specific type of vaccine or booster at once (i.e. wild type or new variant, but not both).
Honestly we need operation warp speed again. It needs to just never stop, at least while we are in such a critical stage and massive amount of virus spread. We need the government and the billionaires/trillionaires to bankroll parallel development of all major variant boosters at once.
> Honestly we need operation warp speed again. It needs to just never stop, at least while we are in such a critical stage and massive amount of virus spread. We need the government and the billionaires/trillionaires to bankroll parallel development of all major variant boosters at once.
This makes sense defense-wise, as well, because the arms race in vaccine development is also an arms race in producing vaccines for diseases you intend to use as weapons. A disease a group has a vaccine or cure for, but no one else does, could be weaponized.
This makes sense defense-wise, as well, because the arms race in vaccine development is also an arms race in producing vaccines for diseases you intend to use as weapons. A disease a group has a vaccine or cure for, but no one else does, could be weaponized.
I agree. Someone please correct me if I’m wrong, but I imagine it’ll be a huge advantage to be able to produce new vaccines at the same rate that a weaponized virus can mutate.
It comes at the cost of reducing regulatory burden but also the oversight and safety rails required to make sure the "cure isn't worse than the disease".
For the initial wave of COVID-19, it was an absolute necessity, but unless our backs are pinned metaphorically to the wall, is it really worth taking a short cut? In the best case, COVID-19 will become endemic (prevalent every season, but not as harmful for the majority of the population)... so wiping it out by way of universal uptake of a given vaccine is not (and never was) on the tables.
A weaponized virus would inflict untold suffering, but there is nothing to stop another Operation Warpspeed. Having OW active all the time? I don't see that being a good thing.
For the initial wave of COVID-19, it was an absolute necessity, but unless our backs are pinned metaphorically to the wall, is it really worth taking a short cut? In the best case, COVID-19 will become endemic (prevalent every season, but not as harmful for the majority of the population)... so wiping it out by way of universal uptake of a given vaccine is not (and never was) on the tables.
A weaponized virus would inflict untold suffering, but there is nothing to stop another Operation Warpspeed. Having OW active all the time? I don't see that being a good thing.
IF I Understand Correctly; this could actually backfire on the entity using it as a weapon by constantly having new vaccines at the ready.
IIUC: This means that they would essentially be supplying the new pressure and stressors required for the virus to be forced into mutating more and more since its current environment is not suitable for its current arrangement. Every time it replicates there is a chance for mutation, but greater stressors increase that chance of mutation. Depending on the stressors, the mutation may or may not occur in tandem to that stressor. I.E. Vaccines increase immunity? Virus gains ability to breakthrough easier.
Now that may be a rather simplistic understanding of it, I admit; but this does seem to coincide with what is essentially happening so far this past couple years.
1. New variant emerges. 2. More people get vaccinated. 3. Old 'new' variant dies off 4. New 'new' variant picks up. 5. More people get vaccinated, or re-vaxxed. 6. Old 'new' variant dies off, again. 7. New variant emerges, or a subvariant, or double mutation. Repeat.
Eventually we will all be vaccinated 3 times or more, easily. Or at least a very large majority of us. What happens when some super variant emerges and has the capability to breakthrough all that resistance?
More vaccines?
You do see where this is going, right? Doctors and scientists were concerned about a very similar situation with anti-bacterial resistant bugs. Stuff like H.Pylori in hospitals if I remember correctly. Well, now we have the same situation potentially occurring on our hands.
We can only hope that the mRNA vaccines or something better is/are able to keep ahead of the game. The only way we are beating this thing out, is by completely snuffing it out. And that's going to require removing all its potential hosts.
That means we might have to vaccinate wild animals, because deer have been catching it for instance. And apparently spreading it in some cases. Once so far for sure is confirmed I believe. So yeah, Deer-vid is a thing now. Hooray?
It's going to be either a lot of animal vaccinations going on out there... or a huge culling. Of all sorts of animals. Or letting them catch it and suffer through it for better resistance for a time being; and then hoping to snuff out the virus finally at that point.
I'm sure you can see how hopeless this all is at this point. It's part of why the politicians are now saying "we need to learn to live with Covid."
And I agree, I guess. Not really much choice at this point. It's here to stay in its current forms, and further. For now at least.
So, huge advantage? Sure, maybe. Depends on your goals.
IIUC: This means that they would essentially be supplying the new pressure and stressors required for the virus to be forced into mutating more and more since its current environment is not suitable for its current arrangement. Every time it replicates there is a chance for mutation, but greater stressors increase that chance of mutation. Depending on the stressors, the mutation may or may not occur in tandem to that stressor. I.E. Vaccines increase immunity? Virus gains ability to breakthrough easier.
Now that may be a rather simplistic understanding of it, I admit; but this does seem to coincide with what is essentially happening so far this past couple years.
1. New variant emerges. 2. More people get vaccinated. 3. Old 'new' variant dies off 4. New 'new' variant picks up. 5. More people get vaccinated, or re-vaxxed. 6. Old 'new' variant dies off, again. 7. New variant emerges, or a subvariant, or double mutation. Repeat.
Eventually we will all be vaccinated 3 times or more, easily. Or at least a very large majority of us. What happens when some super variant emerges and has the capability to breakthrough all that resistance?
More vaccines?
You do see where this is going, right? Doctors and scientists were concerned about a very similar situation with anti-bacterial resistant bugs. Stuff like H.Pylori in hospitals if I remember correctly. Well, now we have the same situation potentially occurring on our hands.
We can only hope that the mRNA vaccines or something better is/are able to keep ahead of the game. The only way we are beating this thing out, is by completely snuffing it out. And that's going to require removing all its potential hosts.
That means we might have to vaccinate wild animals, because deer have been catching it for instance. And apparently spreading it in some cases. Once so far for sure is confirmed I believe. So yeah, Deer-vid is a thing now. Hooray?
It's going to be either a lot of animal vaccinations going on out there... or a huge culling. Of all sorts of animals. Or letting them catch it and suffer through it for better resistance for a time being; and then hoping to snuff out the virus finally at that point.
I'm sure you can see how hopeless this all is at this point. It's part of why the politicians are now saying "we need to learn to live with Covid."
And I agree, I guess. Not really much choice at this point. It's here to stay in its current forms, and further. For now at least.
So, huge advantage? Sure, maybe. Depends on your goals.
How about this : https://www.lesswrong.com/posts/niQ3heWwF6SydhS7R/making-vac....
> The large majority of the cost (about $850) was the peptides
If we could produce just the peptides at scale then everyone is free to produce local vaccines. Not sure if the peptides themselves have the same extreme storage requirements as the vaccines do. If we can give every country the techniques to build their own vaccines we wouldn't depend on mega-corps and some of the "anti-vax" arguments would become moot.
> The large majority of the cost (about $850) was the peptides
If we could produce just the peptides at scale then everyone is free to produce local vaccines. Not sure if the peptides themselves have the same extreme storage requirements as the vaccines do. If we can give every country the techniques to build their own vaccines we wouldn't depend on mega-corps and some of the "anti-vax" arguments would become moot.
isn't omikron acting like a vaccine anyway ? with its astounding spread, everyone will have been contaminated anyway. And it seems that natural immunity is as good if not better than mrna induced immunity ( although i'm not sure if it's controversial or not).
Omikron is milder on average. I had it in February, was hit really hard for 4 days, and then I was more or less good again. But I still have lingering problems like short-breath and heart palpitations, which I am currently in the process of getting diagnosed. Could for example be a myocarditis, or just the typical unspecific "long covid" symptoms resulting from damage to nerves and tissue. Vaccines can have long-term side-effects, too, but in all likelihood at much lower levels.
And the hospitalisation rates for Omikron are still way too high compared to how fast it spreads, at least for most healthcare systems.
And the hospitalisation rates for Omikron are still way too high compared to how fast it spreads, at least for most healthcare systems.
I got my result today morning +ve. Fever wasn’t breaking since last 3 days. It remained 102-103.5F. Today it came down to 99.5F. No other symptoms so far, except on and off body ache and headache.
I hope I get better without having to visit a hospital.
What should I get tested for after getting better?
Did you go for this as routine checkup or after some symptoms, or you wanted to see what damage was caused by COVID?
I hope I get better without having to visit a hospital.
What should I get tested for after getting better?
Did you go for this as routine checkup or after some symptoms, or you wanted to see what damage was caused by COVID?
As is tradition, covid hit me at the absolute worst time, 2 weeks before the end of a project, so I was really stressed out while/after having it. At first I attributed the lingering symptoms like groggyness and irregular/loud heartbeat just to stress, but since it persisted now for 2+ weeks after the end of the most stressful time, I got a bit suspicious and contacted my GP.
I'm gonna do an electrocardiogram next week, and based on that the GP might do some other tests. So you should listen to your body and try to have little stress, no drinking, no hard sports for a few weeks, and contact your GP if you don't feel good.
I'm gonna do an electrocardiogram next week, and based on that the GP might do some other tests. So you should listen to your body and try to have little stress, no drinking, no hard sports for a few weeks, and contact your GP if you don't feel good.
My GP has already prescribed me a chest CT scan as my fever basically didn’t budge for 3.5 days with paracetamol and NISE as well. My CRP was elevated as well.
Now fever is down. My 5th day of symptoms today. I’m going to repeat CRP and then additionally do a chest CT scan today. She will see whether all is well or almost well with me or do I need specific care as of now or later as part of recovery. I think I technically I am still a covid patient.
And god, why is it difficult for every doctor out there to understand and accept that my “normal body temperature is below 98.6 F”!!
Now fever is down. My 5th day of symptoms today. I’m going to repeat CRP and then additionally do a chest CT scan today. She will see whether all is well or almost well with me or do I need specific care as of now or later as part of recovery. I think I technically I am still a covid patient.
And god, why is it difficult for every doctor out there to understand and accept that my “normal body temperature is below 98.6 F”!!
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Even if surviving infection confers immunity similar to one vaccination dose, that's not enough. COVID is so virulent and severe that you want multiple vaccine doses.
1 covid + 1 vaccine seems to be the "best" exposure, since the vaccine only has spike, but the obvious downside is that you catch covid which you really should avoid if you can.
However, it does seem like it's not necessary to make people get 2-3 vaccines if they caught it.
However, it does seem like it's not necessary to make people get 2-3 vaccines if they caught it.
bobdobbs666(4)
No, the problem has been that the variant vaccines have not shown superior responses to variants vs. the original spike isolate in preclinical and small trials.
Incorrect, the beta variant vaccine for example showed quite good strength at stopping the beta variant vs. the wild type vaccine (which beta much more easily evaded). The problem is beta variant grew for a bit last year but is entirely gone now.
We sequenced covid 19 on January 11, 2020. Within 2 days, we have a vaccine. It took 2 months (March 2020) to get that vaccine into humans, and almost an entire year (December 2020) to get an emergency use authorization to use it outside of clinical trials.
Updated vaccines are being looked into, but the original ones still work well enough that there is not the push to expedite the process we saw with the original one. With the virus slowing down to herd immunity, it is likely we won't see another such a push for this pandemic.
Updated vaccines are being looked into, but the original ones still work well enough that there is not the push to expedite the process we saw with the original one. With the virus slowing down to herd immunity, it is likely we won't see another such a push for this pandemic.
reminds me code that takes 1 day to write, 1 week to write tests for, and 2 months to release safely
Or even the two lines of code you wrote after researching the problem/solution for a week.
Bottom of the stack rank for you, slacker.
And a lifetime to maintain.
that entire year was also spent doing process engineering to scale up manufacture and delivery from zero to millions and millions of doses.
my understanding is that going from something in the lab to something that is produced at scale requires significant chemical engineering work, similar to, but likely harder than hardware which is based on parts availability and cost.
all warp speed did was release money and allow process development and testing phases to overlap, is my understanding.
my understanding is that going from something in the lab to something that is produced at scale requires significant chemical engineering work, similar to, but likely harder than hardware which is based on parts availability and cost.
all warp speed did was release money and allow process development and testing phases to overlap, is my understanding.
A couple of reasons
1. It's still pretty effective against COVID
2. Clinical trials showed variant specific versions weren't that much more effective
3. Protecting against the granddaddy strain has a much broader effect than protecting against a new strain.
1. It's still pretty effective against COVID
2. Clinical trials showed variant specific versions weren't that much more effective
3. Protecting against the granddaddy strain has a much broader effect than protecting against a new strain.
Are you sure about #3? That vast majority of cases now are Omicron, so new variants are far more likely to branch off of Omicron than an earlier strain. Therefore I can't imagine how a vaccine targeting the original spike protein would be expected to be more effective than one targeting the spike protein from Omicron against new variants.
One other consideration is that Omicron is significantly milder than previous variants
Perhaps there's a fear that an Omicron targeted vaccine would allow a more deadly variant to take over again
Perhaps there's a fear that an Omicron targeted vaccine would allow a more deadly variant to take over again
> Therefore I can't imagine how a vaccine targeting the original spike protein would be expected to be more effective than one targeting the spike protein from Omicron against new variants.
Well, besides imagining, we're also doing science, so what does the data that you've seen say?
Well, besides imagining, we're also doing science, so what does the data that you've seen say?
Is there data out there comparing variant-specific vaccines to the original in their effectiveness against derivative variants? I haven't seen anything like that.
Perhaps there is a reason the original vaccine would be expected to be more broadly effective, as my parent said. It's not intuitive to me, but that doesn't mean it's wrong. Hence my question.
Perhaps there is a reason the original vaccine would be expected to be more broadly effective, as my parent said. It's not intuitive to me, but that doesn't mean it's wrong. Hence my question.
My point was that our human body doesn't work by rhetorical reasoning or intuition. There are often things we discover about our immune system that are counter intuitive - for e.g. Using specially developed & formulated vaccines to teach the body to suppress immune response towards antigens (via Treg cells), rather than to neutralize them which is what most vaccines aim to do.
Specifically I was objecting to "Given X, we wouldn't expect Y to happen" aspect of your argument. Its never so simple with the human body! It works in many other domains, and so as a former programmer myself I have to catch myself trying to apply such reasoning to biological systems which can't be modeled like that.
Specifically I was objecting to "Given X, we wouldn't expect Y to happen" aspect of your argument. Its never so simple with the human body! It works in many other domains, and so as a former programmer myself I have to catch myself trying to apply such reasoning to biological systems which can't be modeled like that.
Let's say we wait until only 1 out of 10000 cases world-wide is caused by a non-Omicron strain. Then, an Omikron-specific booster would be worth it. Otherwise, we are just playing whack-a-mole with other strains.
What if we had multivalent mRNA vaccines like the HPV vaccine? Gardasil first covered three different strains, then later was bumped to nine, hence Gardasil-9. It doesn’t have to be all or nothing.
HPV viruses are DNA viruses, which means they evolve way slower than Corona viruses. This makes it easier to identify strains that are worth developing a vaccine against. Also, the mRNA technology and/or the production lines are probably not yet capable of producing multivalent vaccines.
There are some in development, but they don't use mRNA.
https://www.technologynetworks.com/vaccines/articles/the-hun...
https://www.technologynetworks.com/vaccines/articles/the-hun...
It's really not effective at all anymore with 12% efficiency [1]. Boosters are only "good" for your own placebo thoughts.
[1] https://www.cnbc.com/2022/02/28/pfizer-covid-vaccine-was-jus...
[1] https://www.cnbc.com/2022/02/28/pfizer-covid-vaccine-was-jus...
Thanks for linking the article, if you had read the title it says "in kids 5 to 11". The 6th sentence notes that "kids 5 to 11" received a lower dosage. It goes on to reference a study that showed dosage matters.
Delete your comment to save face?
Delete your comment to save face?
Boosters of the current vaccine are somewhat effective against hospitalization and death, though even that benefit wears off alarmingly quickly. There's not really any justification for vaccinating 5-11 year olds at this point though given the mediocre benefits and the risk of side effects.
In very young kids at considerably reduced dosage
> Yet after so many mutations of covid, all we have is still the original version of covid mRNA vaccine. Why?
Think of COVID as a human being. The mRNA vaccine teaches your immune system to recognize and destroy hands instead of a whole person. As a result your immune system can detect all shapes and sizes of people as long as they have hands. It is possible for the virus to mutate to use claws instead of hands, but then it isn't as effective at grabbing cells to infect them.
Think of COVID as a human being. The mRNA vaccine teaches your immune system to recognize and destroy hands instead of a whole person. As a result your immune system can detect all shapes and sizes of people as long as they have hands. It is possible for the virus to mutate to use claws instead of hands, but then it isn't as effective at grabbing cells to infect them.
The point was that mRNA vaccines should be able to be quickly adapted to detect claws.
An mRNA vaccine could be designed tomorrow to target claws instead of hands, the issue is how long it takes to test them / get approval to use them, not how long it takes to develop them.
In the case of an incredibly rapidly mutating virus like COVID-19 it's just not worth it to go through that whole process every time it goes from hands to claws to hooves.
In the case of an incredibly rapidly mutating virus like COVID-19 it's just not worth it to go through that whole process every time it goes from hands to claws to hooves.
> it's just not worth it to go through that whole process every time it goes from hands to claws to hooves.
It's not that it's not worth it, it's that this approach doesn't work. Evolution is a remarkable force, and unless there's a good reason for the part of the virus/bacteria/amoeba you're targeting to stay that way, it will change to escape the selective pressure against it. We're more-or-less seeing this with SARS-CoV2, even though the virus is a relative amateur at genetic drift.
OK, you may say "let's target the vaccine against a part that doesn't change"...that's great, except that those parts tend to be so common -- so "evolutionarily conserved" -- that you see them all over the place, including, often enough...your own body. Train your immune system to (over)react against common antigens, and you're going to cause problems.
The primary reason that vaccine development is difficult is because you have an extremely high bar for effectiveness, coupled with an extremely low bar for side-effects. And even if you find such a unicorn target, you have to make sure it stays magical over time. The mRNA technologies are great and do accelerate things, but ultimately, the speed of the Covid vaccine development process was more about our willingness to throw huge money at the problem and eliminate all development and liability risk, than it was about any particular technology platform.
It's not that it's not worth it, it's that this approach doesn't work. Evolution is a remarkable force, and unless there's a good reason for the part of the virus/bacteria/amoeba you're targeting to stay that way, it will change to escape the selective pressure against it. We're more-or-less seeing this with SARS-CoV2, even though the virus is a relative amateur at genetic drift.
OK, you may say "let's target the vaccine against a part that doesn't change"...that's great, except that those parts tend to be so common -- so "evolutionarily conserved" -- that you see them all over the place, including, often enough...your own body. Train your immune system to (over)react against common antigens, and you're going to cause problems.
The primary reason that vaccine development is difficult is because you have an extremely high bar for effectiveness, coupled with an extremely low bar for side-effects. And even if you find such a unicorn target, you have to make sure it stays magical over time. The mRNA technologies are great and do accelerate things, but ultimately, the speed of the Covid vaccine development process was more about our willingness to throw huge money at the problem and eliminate all development and liability risk, than it was about any particular technology platform.
> The mRNA technologies are great and do accelerate things, but ultimately, the speed of the Covid vaccine development process was more about...
Nope, the Moderna vaccine was designed in 2 days after getting a full DNA sequencing of the virus. Very rapid design is a particular feature of mRNA vaccines (with the caveat that sequencing to find the right proteins is required).
Nope, the Moderna vaccine was designed in 2 days after getting a full DNA sequencing of the virus. Very rapid design is a particular feature of mRNA vaccines (with the caveat that sequencing to find the right proteins is required).
Yes, as I said, the technology accelerates things somewhat. But to put it in a computer science context, it's like slightly reducing the constant on an O(n^3) algorithm. You're making things faster, sure, but you're not really going to affect the time to create a vaccine.
Said differently: the slow part of creating a vaccine is doing the trials to make sure you have safe and effective target.
Said differently: the slow part of creating a vaccine is doing the trials to make sure you have safe and effective target.
Yes, that was literally the point I made in the first comment. Not sure what we're arguing about.
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The vaccines can quickly adapt, but the process of proving each version safe to use takes time each time.
Because there is no need for an updated vaccine. The original vaccine (especially with a booster 6 months after the second dose) is extremely effective at preventing severe disease, hospitalization, and death for all variants of SARS-CoV-2. (Alpha, Beta, Delta, Omicron, etc)
Nope. See https://www.nejm.org/doi/full/10.1056/NEJMoa2200797
The conclusion said it is less effective.
The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19–related hospitalization and death. (Funded by Weill Cornell Medicine–Qatar and others.)
Don't get me wrong, I believe in the vaccine, but I think we are still far away from one vaccine that kill all the the mutations.
The conclusion said it is less effective.
The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19–related hospitalization and death. (Funded by Weill Cornell Medicine–Qatar and others.)
Don't get me wrong, I believe in the vaccine, but I think we are still far away from one vaccine that kill all the the mutations.
From the link you posted:
In this study, mRNA boosters were highly effective against infection with the delta variant but were less effective against infection with the omicron variant. However, these boosters led to strong protection against Covid-19–related hospitalization and death due to both variants.
We vaccinate in order to prevent severe disease, hospitalization, and death. The original vaccines, per the link you shared, are extremely effective at this.
In this study, mRNA boosters were highly effective against infection with the delta variant but were less effective against infection with the omicron variant. However, these boosters led to strong protection against Covid-19–related hospitalization and death due to both variants.
We vaccinate in order to prevent severe disease, hospitalization, and death. The original vaccines, per the link you shared, are extremely effective at this.
Originally, the plan was to vaccinate in order to obtain herd immunity and wipe out COVID.
Smart people adjust plans as they discover new information. Your original hopes for a solution at the start of a disaster will change drastically as you better understand the problem at hand.
There seems to be a pervasive thought that our leaders ought to somehow become superhuman and obtain clairvoyance about how to solve any problem we have. They are no different from any of us, who think a bug has a simple solution before we spend a lot of time figuring out more complicated things were happening under the hood.
There seems to be a pervasive thought that our leaders ought to somehow become superhuman and obtain clairvoyance about how to solve any problem we have. They are no different from any of us, who think a bug has a simple solution before we spend a lot of time figuring out more complicated things were happening under the hood.
"Smart people adjust plans as they discover new information."
The new information, that the world is globalized, with many countries not being able to afford vaccines and also many militant anti vaxxers around?
How was wiping out covid, a realistic goal in the first place?
The new information, that the world is globalized, with many countries not being able to afford vaccines and also many militant anti vaxxers around?
How was wiping out covid, a realistic goal in the first place?
The problem isn't really affording vaccines so much as being able to administer them. Africa is a big place; it is literally hard to get very cold mRNA vaccines to people even if we donate them.
Similarly, a lot of people have been claiming we're evilly withholding patents from the world, but that can't be a real issue or China and Russia would just have stolen the IP from us. They literally can't produce them any faster even with the rights.
Similarly, a lot of people have been claiming we're evilly withholding patents from the world, but that can't be a real issue or China and Russia would just have stolen the IP from us. They literally can't produce them any faster even with the rights.
We managed to keep SARS and MERS fairly contained.
But I believe that was a very different situation at that time, with it not already spread globally and being less infectious.
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Actually originally the plan was to hope for 50% efficacy, even knowing that coronavirus immunity may wane after several months as is the case with seasonal coronaviruses
Less effective doesn’t mean it isn’t extremely effective. Lightbulbs are less effective at providing light than the sun but they’re still extremely effective providers of light.
This analogy made me smile :-)
There is no disagreement between your comments.
That's the wrong comparison though, you would need to compare a wild type booster vs an omicron specific booster.
Unfortunately the public was told last year that the vaccines were near perfect and vaccinated people wouldn't get sick. Here's the head of the CDC at the time saying vaccinated people "do not carry the virus" and were 90% protected against infection: https://www.businessinsider.com/cdc-director-data-vaccinated...
The CDC needs to be explicit and clearly admit that it was wrong or the data changed, and that vaccinated/boosted people can and will get sick or even spread disease to others. The new 'deal' is that they will likely not be hospitalized or suffer severe disease if infected.
Far too many people are still walking around thinking their shots and booster, now nearly 6 months old for some, are an impenetrable force field against any sickness.
The CDC needs to be explicit and clearly admit that it was wrong or the data changed, and that vaccinated/boosted people can and will get sick or even spread disease to others. The new 'deal' is that they will likely not be hospitalized or suffer severe disease if infected.
Far too many people are still walking around thinking their shots and booster, now nearly 6 months old for some, are an impenetrable force field against any sickness.
Have you read your own article?
Yes, it says "On Monday, the CDC released a study finding mRNA vaccines __90% effective at preventing infection__."
I remember last year when this news hit, that bit about 90% effective *against infection* was amplified and played nonstop for the public. The message was clearly get vaccinated and you will not get sick.
It was not until July and the CDC MMWR report on the Providence, Rhode Island, bear week festivities that lead to unexpected breakthrough infections that the CDC admitted the vaccines were not 90% effective against infection anymore. Unfortunately this updated message has never been clearly told to the public, at least not as clearly or loudly as the original 90% protection against infection message.
I remember last year when this news hit, that bit about 90% effective *against infection* was amplified and played nonstop for the public. The message was clearly get vaccinated and you will not get sick.
It was not until July and the CDC MMWR report on the Providence, Rhode Island, bear week festivities that lead to unexpected breakthrough infections that the CDC admitted the vaccines were not 90% effective against infection anymore. Unfortunately this updated message has never been clearly told to the public, at least not as clearly or loudly as the original 90% protection against infection message.
From the Business Insider article you posted:
> Walensky was referring to a new CDC study of nearly 4,000 front-line workers, some vaccinated and some not, who tested themselves weekly for COVID-19 infections between December and March.
> But more data is still necessary to say so definitively, which is why researchers are recruiting thousands of college students across the country to find out more about the likelihood of asymptomatic spread of this virus among vaccinated people.
The article is explicit that the CDC was talking about the findings in a new study, and that more research still needed to be conducted before being sure of their findings.
> It was not until July and the CDC MMWR report on the Providence, Rhode Island, bear week festivities that lead to unexpected breakthrough infections that the CDC admitted the vaccines were not 90% effective against infection anymore.
Because of the new delta variant that those very same festivity goers helped the CDC with[1], and that changed the CDC's guidelines:
> The speed of the investigation — and the exceptional participation from the mostly gay men involved in the outbreak — helped the CDC learn new information about the delta variant. And it was that new information, in part, that prompted the agency to change its guidance for how vaccinated people should keep themselves safe at this stage of the pandemic — including a return to masking indoors.
[1] https://www.npr.org/sections/health-shots/2021/08/06/1025553...
> Walensky was referring to a new CDC study of nearly 4,000 front-line workers, some vaccinated and some not, who tested themselves weekly for COVID-19 infections between December and March.
> But more data is still necessary to say so definitively, which is why researchers are recruiting thousands of college students across the country to find out more about the likelihood of asymptomatic spread of this virus among vaccinated people.
The article is explicit that the CDC was talking about the findings in a new study, and that more research still needed to be conducted before being sure of their findings.
> It was not until July and the CDC MMWR report on the Providence, Rhode Island, bear week festivities that lead to unexpected breakthrough infections that the CDC admitted the vaccines were not 90% effective against infection anymore.
Because of the new delta variant that those very same festivity goers helped the CDC with[1], and that changed the CDC's guidelines:
> The speed of the investigation — and the exceptional participation from the mostly gay men involved in the outbreak — helped the CDC learn new information about the delta variant. And it was that new information, in part, that prompted the agency to change its guidance for how vaccinated people should keep themselves safe at this stage of the pandemic — including a return to masking indoors.
[1] https://www.npr.org/sections/health-shots/2021/08/06/1025553...
Unfortunately, that would destroy the narrative that the CDC is infallible and everyone should unquestioningly follow their advice, always.
Btw, I’ve had both shots, had COVID and will get the booster.
Btw, I’ve had both shots, had COVID and will get the booster.
Noone has ever thought the CDC was infallible; we traditionally ignore everything public health officials tell us to do, since it's mainly things like "never eat medium-rare hamburgers".
That is unfortunate that we switched to directly getting mask policies etc. from them, because it's not their job to consider tradeoffs and they aren't good at it.
That is unfortunate that we switched to directly getting mask policies etc. from them, because it's not their job to consider tradeoffs and they aren't good at it.
I've never heard that narrative, except from people into anti-establishment attacks who are criticizing the narrative. It's a strawperson, IME.
is strawman so non inclusive and offensive in the US?
Come to think of it, I'm not sure I've ever seen a strawwoman. Maybe as part of a straw couple as decoration at a harvest market or something
Well ok they'll get sick. People get sick. They'll get way less sick, so that's good!
> that vaccinated/boosted people can and will get sick or even spread disease to others
Are you under the impression this isn't what they've been telling people?
The article I posted has a quote and video of the director of the CDC explicitly saying in March of last year that vaccinated people "do not carry the virus" and were 90% protected __against infection__.
That's a direct quote from the head of the CDC, it does not get more official or more of a primary source than that IMHO.
That's a direct quote from the head of the CDC, it does not get more official or more of a primary source than that IMHO.
It actually does get more official than a director's spoken words, but moot point. You are writing as if in the year since that largely pre-Delta point in time that the CDC's official guidance was that you won't carry the virus and are protected from infection — and it was never updated.
In randomized clinical trials, the original mRNA vaccines were just as effective as modified versions at preventing symptomatic disease and hospitalization due to SARS-CoV-2 infection
This isn't true. No RCTs have ever been performed on the original vaccines and the subsequent variants. And to the extent that other kinds of experiments (retrospective cohort studies, etc.) have been done, they've almost universally found diminished effectiveness against mild illness.
Effectiveness of the original vaccines against Omicron infection, in particular, is essentially zero after a few months:
https://www.medrxiv.org/content/10.1101/2021.12.20.21267966v...
It should be noted that the vaccines appear to remain highly effective against severe illness, even without boosting. The mRNA vaccines, in particular, seem to raise a robust, long-lasting cellular immune response, even though antibody levels rapidly fall. One of the downsides of the unusually rapid approval process for the Covid vaccine was that it was impossible to see this pattern in a randomized trial that lasted only a few months. This led "experts" -- people who really should have known better -- to oversell the shots as a form of sterilizing immunity. They are not.
There are good reasons vaccines take a long time to develop.
Effectiveness of the original vaccines against Omicron infection, in particular, is essentially zero after a few months:
https://www.medrxiv.org/content/10.1101/2021.12.20.21267966v...
It should be noted that the vaccines appear to remain highly effective against severe illness, even without boosting. The mRNA vaccines, in particular, seem to raise a robust, long-lasting cellular immune response, even though antibody levels rapidly fall. One of the downsides of the unusually rapid approval process for the Covid vaccine was that it was impossible to see this pattern in a randomized trial that lasted only a few months. This led "experts" -- people who really should have known better -- to oversell the shots as a form of sterilizing immunity. They are not.
There are good reasons vaccines take a long time to develop.
From the article I read[1], the nuance was along the line of this -- a person who was previously exposed to the original COVID vaccine or the virus itself (and had an immune response) getting the updated version of the vaccine ends up having the immune response for the _original_ antigen[2], rather than the new one.
Since the immune response is for the older versions of the virus, getting the updated vaccine still ends up having the same effectiveness of the original vaccine.
[1]: https://arstechnica.com/science/2022/02/monkey-study-casts-d...
[2]: https://en.wikipedia.org/wiki/Original_antigenic_sin
Since the immune response is for the older versions of the virus, getting the updated vaccine still ends up having the same effectiveness of the original vaccine.
[1]: https://arstechnica.com/science/2022/02/monkey-study-casts-d...
[2]: https://en.wikipedia.org/wiki/Original_antigenic_sin
Yeah, an immune response specific to the Omicron variant would likely be more effective against Omicron for obvious reasons, but it's probably not possible to get one in people with immunity to older variants because their existing immunity gets in the way. This isn't too surprising - it's one of the things that seems to limit the effectiveness of the flu vaccine.
While it is easy to modify, it still takes time to test the modified vaccine. The vaccines were designed to target the spike protein which is shaped to allow it to enter human cells. If that protein evolved too much to evade the vaccine, it would also become less effective in entering human cells.
In the future they might prepare a wide number of vaccines targeting common coronavirus ahead of time so there can be quick response when an outbreak appears.
In the future they might prepare a wide number of vaccines targeting common coronavirus ahead of time so there can be quick response when an outbreak appears.
In monkeys, there wasn't much of a benefit of an omicron specific booster vs an original Wuhan strain booster. The main thing was just getting a third dose which generates the mature antibodies that are apparently similar enough between current variants.
Not exactly sure, but I think the original version of the covid vaccine has been good enough for the mutations and there has not been need for modified version.
We don't know if it's worth updating the covid vaccine, because updating it to be more like omicron would make it less like the original type, and we don't think that's a worthwhile tradeoff.
The answer is a "pancoronavirus" vaccine that'd work against all of them, but it seems that using mRNA or not doesn't actually help with that.
The answer is a "pancoronavirus" vaccine that'd work against all of them, but it seems that using mRNA or not doesn't actually help with that.
Previous to this the record for fastest vaccine was 4 years, so I'd say promise is kept (Zika vaccine was on a path to beat the 4 year mark but COVID vaccine would still be faster). Vaccines normally take years to develop
Without the initial covid urgency there is an insane red tape beurocracy on new vaccines. It takes 7 years for the average vaccine to be approved and its 90% avoidable busywork.
I'm not so sure it's busy-work.
There's a prioritisation issue. There are so many diseases, and many more proposed treatments. Without a good reason to jump the queue there are bound to be delays.
There's also the efficacy testing issue. Your phase 2/phase 3 test subjects are mostly young european males (Uni-students). Without deliberately exposing them, how likely are they (and the control group) get infected? It could take years for a statistically significant number of the control group to catch the disease.
When there's a pandemic on you might hit those numbers in a few weeks.
There's a prioritisation issue. There are so many diseases, and many more proposed treatments. Without a good reason to jump the queue there are bound to be delays.
There's also the efficacy testing issue. Your phase 2/phase 3 test subjects are mostly young european males (Uni-students). Without deliberately exposing them, how likely are they (and the control group) get infected? It could take years for a statistically significant number of the control group to catch the disease.
When there's a pandemic on you might hit those numbers in a few weeks.
My cynical take: New versions of the mRNA vaccine were unable to change the first two vaccine's "original antigenic sin".
That's dengue. It doesn't appear that getting covid makes it even worse the next time you get it. (I have seen people say this, but they're also saying wild stuff like "everyone who gets covid ends up with dementia".)
C'mon, you can't just throw out a number like that and not provide an exhaustive list of all 15 targeted diseases!
The article (and its linked source) mentions Chikungunya, Crimean-Congo hemorrhagic fever, Dengue, Ebola, Malaria, Marburg, Lassa fever, MERS, and COVID-19. Reading through the articles in depth also reveals mentions of Nipah, HIV, and Tuberculosis. That's 12. So what are the other 3?
The article (and its linked source) mentions Chikungunya, Crimean-Congo hemorrhagic fever, Dengue, Ebola, Malaria, Marburg, Lassa fever, MERS, and COVID-19. Reading through the articles in depth also reveals mentions of Nipah, HIV, and Tuberculosis. That's 12. So what are the other 3?
Dengue has 4 "variants". So that may be those are the other 3?
The thing with dengue is the first time sucks but catching a second variant is often fatal.
The thing with dengue is the first time sucks but catching a second variant is often fatal.
Can anyone explain to me what exactly changed here? As far as i understand it there was nearly zero development effort necessary for COVID. The stuff was basically sitting on a shelf. Yet if i look at older news coverage, it was already clear that once it works, we will basically get a cancer vaccine soon.
edit: The best i can tell its Bayers take on the topic, gene/cell therapy being bad PR. https://youtu.be/OJFKBritLlc?t=5850
edit: The best i can tell its Bayers take on the topic, gene/cell therapy being bad PR. https://youtu.be/OJFKBritLlc?t=5850
I understand the "cancer vaccine" is actually an enormous simplification. There are certain cancer types that can be triggered by viruses, so a vaccine against these viruses could prevent those particular cancer types. But giving the impression that a general vaccine against cancer is somewhere near seems very misleading.
I'm completely out of my depth when it comes to medical research, but the way I understood the mRNA vaccines against cancer types was a bit more broader than what you suggest: Specific cancer cells produce unique proteins that can be targetted by a "vaccine", so as to enable the body to directly attack the mutated cells. I put vaccine in quotation mark, as it rather seems to be a type of mRNA therapy.
Different approaches just like for prophylactic vaccines, in some cases it's just like an old-school vaccine where dead cells or protein antigen is presented, but yeah cancer vaccines are typically therapeutic rather than prophylactic.
Usually what is meant by 'cancer vaccine' isn't the HPV or Hep.B vaccine where the target is the viral causative agent of cancer. They are typically therapeutic rather than prophylactic, inducing immunity against cancer-specific antigens to overcome the immune evasion mechanisms cancer cells use, tog get the relevant elements of the immune system to attack cancer cells directly. Several are already approved, but no one inn the know is saying that a cure-all cancer vaccine is around the corner, cancers are very diverse and the vaccine approach may only be applicable in very niche cases where cancer antigens are sufficiently different enough from normal proteins expressed by healthy cells — and just like targets of immunotherapy and chemotherapy, there's no promising that cancers won't evolve to overcome therapeutics.
The research was easy, but the development required billions of dollars and literal war-time production efforts (in the US the Defense Production Act was invoked). Drug regulators are also very conservative. Why take risk on making a low-margin mRNA influenza vaccine when other platforms are good enough?
I think a lot of it is that clinical trials are expensive and drug manufacturers generally try to maximize odds of success. COVID was unique because they could get a ton of money to develop and test a vaccine that they knew there would be a ton of demand for if they were early to market with something that worked. now that they've seen how much easier and cheaper mRNA vaccines can be to develop, it's much easier to decide to start a trial.
Full disclosure - I have a long-term (sub $10K) holding of Moderna shares.
The best explanation I've heard for it; is that given by Stephane Bancel (Moderna's CEO) to the (excellent) Bio Eats World podcast in the episode "The Machine That Made the Vaccine" (https://bio-eats-world.simplecast.com/episodes/moderna-covid...)
His explanation goes something like this [0] ...
1) If developers have target protein(s) they know they need to get the body's cells to synthesise to fight disease. Then the key advantage of mRNA technology is that it makes activating this a _turnkey_ operation.
2) With Covid-19, humanity got lucky, the target protein(s) were identified very early in the pandemic, and they have remained useful [1].
These, combined, allowed them to construct a viable vaccine quickly (days) before they had any physical access to the virus. [3]
These new announcements are for diseases where targets are similarly well-identified (and promising from a therapeutic pov). I think the potential for this technology to improve the human condition is, to put it mildly, incredible.
[0] I'm an SW engineer, and it's been over a year since I listened to the podcast, so apologies to anyone if I mangle this.
[1] For some diseases, this is apparently not the case, e.g. AIDS
[3] Of course it then needed the same standard, thorough acceptance process, albeit accelerated by running parts in parallel, before being released to the general public.
The best explanation I've heard for it; is that given by Stephane Bancel (Moderna's CEO) to the (excellent) Bio Eats World podcast in the episode "The Machine That Made the Vaccine" (https://bio-eats-world.simplecast.com/episodes/moderna-covid...)
His explanation goes something like this [0] ...
1) If developers have target protein(s) they know they need to get the body's cells to synthesise to fight disease. Then the key advantage of mRNA technology is that it makes activating this a _turnkey_ operation.
2) With Covid-19, humanity got lucky, the target protein(s) were identified very early in the pandemic, and they have remained useful [1].
These, combined, allowed them to construct a viable vaccine quickly (days) before they had any physical access to the virus. [3]
These new announcements are for diseases where targets are similarly well-identified (and promising from a therapeutic pov). I think the potential for this technology to improve the human condition is, to put it mildly, incredible.
[0] I'm an SW engineer, and it's been over a year since I listened to the podcast, so apologies to anyone if I mangle this.
[1] For some diseases, this is apparently not the case, e.g. AIDS
[3] Of course it then needed the same standard, thorough acceptance process, albeit accelerated by running parts in parallel, before being released to the general public.
Once you get the genetic sequence sequence you want, you can "print" out the vaccine. After BioNTech received the genetic sequence of SARS-CoV-2 in email, they had small batch vaccine candidates out ready for animal testing within days.
There are still other steps that take time. You need to figure out what is the mRNA you want, then you need to test a new vaccine candidates for adverse effects.
There are still other steps that take time. You need to figure out what is the mRNA you want, then you need to test a new vaccine candidates for adverse effects.
It would have taken many years to get the new technology approved, but we skipped a lot of that due to the pandemic. Now that we have lots of safety data it is easier for them to get new vaccines approved.
Most of the years skipped though was red tape, bureaucratic slog, fundraising, clinical trial participant recruiting, and having a high enough absolute risk of infection in the population that it was not long at all to have a significant difference in effect between treatment arms.
It probably helps that there's now a well develiped framework for mRNA and adenovirus vector vaccine approval, but ultimately any new antigen could certainly be unsafe and future candidates are going to require every bit as much testing and won't get most of the expeditiory benefits the first generation of COVID vaccines experienced.
It probably helps that there's now a well develiped framework for mRNA and adenovirus vector vaccine approval, but ultimately any new antigen could certainly be unsafe and future candidates are going to require every bit as much testing and won't get most of the expeditiory benefits the first generation of COVID vaccines experienced.
Is that really possible with dengue? The vaccine exists now, but it might actually make you more sick.
I live in a country where dengue is a horrible threat, so that would be amazing.
I live in a country where dengue is a horrible threat, so that would be amazing.
Yes. Dengvaxia is a traditional vaccine which uses weakened virus (and which is why it should only be used on people who've been previously infected). The way mRNA vaccines work is that they tell the cells' ribosomes to manufacture a protein segment from the virus which then triggers the immune response by the cells so that the cells are prepared for the actual arrival of the virus.
The article goes into this with more clarity, depth and accuracy than my capsule summary above.
The article goes into this with more clarity, depth and accuracy than my capsule summary above.
Yes but the problem with dengue is antibody mediated enhancement.
Basically people develop antibodies that make future infections worse by potential infections the infectious proteins.
The challenge is not creating a vaccine that stimulates an immune response, the challenge is avoiding a response that makes things worse.
Basically people develop antibodies that make future infections worse by potential infections the infectious proteins.
The challenge is not creating a vaccine that stimulates an immune response, the challenge is avoiding a response that makes things worse.
No idea really but maybe there are specific proteins in the virus that are responsible for this behavior that could be omitted from the vaccine while still finding an effective surface feature to work against?
> The challenge is not creating a vaccine that stimulates an immune response, the challenge is avoiding a response that makes things worse.
Agreed. This is probably always true, there’s just more concrete evidence of this potential outcome with dengue.
> The challenge is not creating a vaccine that stimulates an immune response, the challenge is avoiding a response that makes things worse.
Agreed. This is probably always true, there’s just more concrete evidence of this potential outcome with dengue.
If you never had dengue before, wouldn’t you always have the same response due to vaccine mediated original antigenic sin?
It’s been a while since my immunology courses, but I’ll give it a go.
Antibody response is not necessarily the same, even in the same person with the same antigen.
The immune system basically creates a ton of random antibodies and when they “hit” on the previously unseen antigen, they are amplified.
Now once someone has had an immune response and generated memory cells, then yes, very similar antigens (that somewhat bind to the exist ones the body made prior) will tend to “narrow down” the antibodies generated to varieties of the original one (the immune system basically says ‘these old antibodies are close, so let’s create variation off them to optimize the new ones’).
Then the other thing to consider is that there are different strains of dengue - so you could get type A, generate a response, but then exposed to type B where your type A antibodies activate the infection mechanism rather than disable it.
Antibody response is not necessarily the same, even in the same person with the same antigen.
The immune system basically creates a ton of random antibodies and when they “hit” on the previously unseen antigen, they are amplified.
Now once someone has had an immune response and generated memory cells, then yes, very similar antigens (that somewhat bind to the exist ones the body made prior) will tend to “narrow down” the antibodies generated to varieties of the original one (the immune system basically says ‘these old antibodies are close, so let’s create variation off them to optimize the new ones’).
Then the other thing to consider is that there are different strains of dengue - so you could get type A, generate a response, but then exposed to type B where your type A antibodies activate the infection mechanism rather than disable it.
Yes that's how it works in general, but the article lists dengue and doesn't explain why a protein segment would be safer than what we have now.
Current vaccine is an actual virus, just a weakened (attenuated) version. mRNA vaccine causes your body to create the proteins that your immune system can target if it encounters the actual virus. That allows your immune system to train on the targets without introducing an actual virus. The mRNA version doesn't have the ability to infect a cell and use it to reproduce, it ONLY triggers the immune system.
By eliciting responses against specific parts of a specific protein that minimizes the production of antibodies that bind to, but not neutralize denguevirus.
See also https://pubmed.ncbi.nlm.nih.gov/33194810/ .
See also https://pubmed.ncbi.nlm.nih.gov/33194810/ .
Dengue is the worst. I got hemorrhagic dengue last year and it knocked me on my ass for good.
I’m thankful I had access to good healthcare, otherwise I wouldn’t have had good luck with it.
I also had Chikungunya virus once when I was little. Not fun. We need to eradicate these diseases for good.
I’m thankful I had access to good healthcare, otherwise I wouldn’t have had good luck with it.
I also had Chikungunya virus once when I was little. Not fun. We need to eradicate these diseases for good.
Some of these diseases are not so common. What about diseases like herpes or epstein barr? They don't usually kill but cause endless suffering for billions of people. There is some evidence they can even lead to cancer and dementia.
You are downvoted I guess because of the not common sentence (not exactly sure as you even say some of them)? But I only heard of epstein barr from House (or ER, not entirely sure; some US show anyway) and started reading; seems herpes is connecting all these (at least here) puberty things like mono and different types of herpes and indeed ebv. They all apparently are herpes viruses and indeed, like you say can cause an array of cancers (dementia I could not find but the cancer link was made in a lot of scientific and gov papers). So herpes is rather important to destroy as it (and that included ebv) never goes away and 90%+ people have it. Which makes it easy to make the joke ‘these days everything causes cancer’ which is probably true because if you get old enough, you will develop cancer, but it does not mean we should not try to prevent some of the ways it works. So anyway, never thought ebv is common as I never heard of it in my country but that is because it is confused or piled on with mono (seems the symptoms are similar) and I know quite a lot more about herpes in general. So thanks and you are right; let’s do something about it, but also about the other diseases they mention as they are common in some country; all my Vietnam colleagues and their family had Dengue for instance and it is not good.
Here’s a thread and subreddit on all the efforts for herpes:
https://www.reddit.com/r/HerpesCureResearch/comments/kg66ds/...
Huh. They are crowdfunduing vaccine research? That seems a bit red flag. I would assume if it was actually promising, given the potential market, that funding would be easy to come by. Am i missing something here?
On the other hand, if they needed $500k, this is well within the budget of popular crowd funding projects, and it seemed like they have succeeded. As far as I know they raised the funds so I guess the strategy was sound. I don’t know the details but often crowd funding allows the creators to keep all IP rights, which would give them more freedom than going through institutional investors.
My (uneducated) guess: Some diseases might be "low hanging fruits" for mRNA vaccines (e.g. because they actually use RNA in their attack vector). Other diseases might not use RNA in their attack vector and might therefore not be suitable to be treated with mRNA vaccines.
Some are low hanging fruit because training the immune system on a single specific protein antigen is sufficient to induce immunity. I don't think the RNA is too big of a deal because ultimately its role in the vaccine is to get cells to produce a protein for the immune system to attack, not induce immunity itself.
Effort is going to go to diseases that they reckon have a high probability of success with just by presenting specific antigens. Herpes has had vaccine candidates in clinical trials that failed, chewing through hundreds of millions of dollars along the way. Difficult disease because of the way the virus goes dormant inside of nerve cells, and trials would be expensive and take a very long time because exposure is slow and generally takes years.
While development of a new vaccine-delivery platform is exciting, I think it's important to take this announcement into perspective.
The main problem with producing vaccines is not principally the delivery platform, but the difficulty in generating a sensitive, specific, and effective immune response to your target bug. This problem has plagued immunology for decades (and is a bit of a black art), and sadly may not be solved simply by using mRNA.
Nevertheless, promising news. Presumably this is funded at least in part by the significant profits Modena has generated from the COVID vaccine.
The main problem with producing vaccines is not principally the delivery platform, but the difficulty in generating a sensitive, specific, and effective immune response to your target bug. This problem has plagued immunology for decades (and is a bit of a black art), and sadly may not be solved simply by using mRNA.
Nevertheless, promising news. Presumably this is funded at least in part by the significant profits Modena has generated from the COVID vaccine.
Can't wait for these vaccines to cause a bizarre and ever-changing set of symptoms that will conveniently dissappear as the contrarians get bored on Twitter.
1. The tech platforms finally reneged on their promise to be free speech havens and took an explicitly pro-vaccine stance, suppressing accurate information and promoting disinformation in the process.
2. The anti-this-particular-vaxxers for the most part have won. Vaccine and mask mandates have been dropped just about everywhere.
3. COVID's over, baby. You guys talk about Ukraine now.
moderna has invented a vaccine platform on mrna. they started with covid and have proven they can target diseases using this platform. so keeping the delivery mechanism the same, they are targeting many other diseases.
but was it successful? the covid vaccine loses effectiveness after 8-12 weeks. i don’t know if this is specific to sars-cov-2 and it’s mutations or the mrna delivery platform.
but was it successful? the covid vaccine loses effectiveness after 8-12 weeks. i don’t know if this is specific to sars-cov-2 and it’s mutations or the mrna delivery platform.
The wanning effectiveness was still going from "amazing" to "just ok". "Just ok" is still a really big impact and a lot more than nothing, so its not like it becomes worthless or anything.
It's more that sars-cov-2 is just a nasty virus with exceptionally good skills at evading the immune system, not that mRNA vaccine tech doesn't work after a few months. From what I understand covid-19 can suppress the immune system response and replicate before your body can really detect or react to it. It's only if you have a recent supply of covid-19 spike protein antibodies floating around your blood, like if you were recently vaccinated/boosted, that your immune system can get a faster alarm and head start at clearing a real infection.
So really any vaccine mRNA or not that's targeting the spike protein is going to see similar waning efficacy against infection. We see this with the Johnson and Johnson and Astrazenica shots which don't use mRNA tech for example.
So really any vaccine mRNA or not that's targeting the spike protein is going to see similar waning efficacy against infection. We see this with the Johnson and Johnson and Astrazenica shots which don't use mRNA tech for example.
Another counterexample is the flu vaccine. It never purports to eradicate flu, but it helps with the season. The unfortunate reality is that some diseases change and evolve quickly enough that the immune system can’t defeat every new variant, even with bolstered protection against previous ones. Like you’ll catch a cold from time to time, or perhaps the flu. The immunity you developed previously didn’t stop that because the disease evolved.
If they can do for other diseases what they did for COVID— significantly reducing severity— it’d be a huge win even if it wasn’t inoculating.
I wonder if they carry the same serious side effect risk of the mRNA covid vaccines that are currently available: (permanent) heart damage, death and persistent long covid like side effects. Maybe a whole new set of them?
I would love to get a safe and effective HIV vaccine, but I wouldn‘t take it if it could give me a heart attack!
I would love to get a safe and effective HIV vaccine, but I wouldn‘t take it if it could give me a heart attack!
While solving these diseases is a long shot, this is a fantastic tech and financial reinvestment into improving quality of life for all people. I’m excited to see which discoveries they make, even if the MRNA path isn’t the right one for some of these diseases
So amazing. Hopeful they'll eventually expand to include many other diseases.
xdennis(1)
vbilopav(3)
We're injecting people with rna that induces viral fragment production in human cells. And typically these proteins tend to be inflammatory, they have to be to stimulate the immune system, no?
It won't surprise me to hear down the line that something subtle went wrong in a sizeable proportion of injectees, and that maybe we rushed into this without taking the time to gather longer term data. Think long term immune disorders, which are difficult to diagnose, especially early on.
It wouldn't exactly be the first time we've screwed up.
It won't surprise me to hear down the line that something subtle went wrong in a sizeable proportion of injectees, and that maybe we rushed into this without taking the time to gather longer term data. Think long term immune disorders, which are difficult to diagnose, especially early on.
It wouldn't exactly be the first time we've screwed up.
We’re doing exactly the same as we’re doing with traditional vaccines, but more efficiently. There’s a lot about your comment that misses the subtleties and mechanics of how the immune system works and repeats fears that, quite frankly, stem from ideologically driven falsehoods.
How is it same? I thought traditional vaccines are about injecting the diluted viral load to trigger immune response whereas mRNA vaccine is about injecting rna fragment that hijack your body cell to make the foreign protein to trigger immune response.
Isn't the whole mechanism different?
> about injecting the diluted viral load to trigger immune response
A “diluted viral load” is a very unsafe vaccine. “diluted” means “less of” and basically means infect ourself “with less of the virus” and hope for the best. The virus by definition is an unsafe mRNA payload (sometimes the virus will first burrows into our DNA which then creates the mRNA) that will hijack our cells and reproduce itself until there is a large enough viral load that can trigger immune response.
For an effective and safe “old-school” vaccine we would need a “dead or disabled large viral load”. “dead or disabled” typically means “can’t reproduce” and/or “can’t produce the problem viral proteins” and basically means the amount of virus in our bodies at all times is roughly the amount in the injection. This has to be a large enough “viral load” to trigger immune response.
The new mRNA vaccines are attempting to be safe mRNA payloads pretending to be the unsafe virus by using very small parts of the unsafe virus (e.g. only the spike protein) but this safe mRNA payload will “reproduce” inside our cells creating a lot of spike protein. They create a large enough “viral load” to trigger immune response.
There is no body without mRNA and there are basically no viruses that don’t leverage mRNA and therefore all previous vaccines used mRNA we just didn’t have good technology to use it directly.
I hope this helps clarify that “diluted viral load” is an incorrect oversimplification for old/new vaccine science. To understand “old school” vaccines, you would be better off with “boiled viral load” or “cooked viral load” as the oversimplification.
A “diluted viral load” is a very unsafe vaccine. “diluted” means “less of” and basically means infect ourself “with less of the virus” and hope for the best. The virus by definition is an unsafe mRNA payload (sometimes the virus will first burrows into our DNA which then creates the mRNA) that will hijack our cells and reproduce itself until there is a large enough viral load that can trigger immune response.
For an effective and safe “old-school” vaccine we would need a “dead or disabled large viral load”. “dead or disabled” typically means “can’t reproduce” and/or “can’t produce the problem viral proteins” and basically means the amount of virus in our bodies at all times is roughly the amount in the injection. This has to be a large enough “viral load” to trigger immune response.
The new mRNA vaccines are attempting to be safe mRNA payloads pretending to be the unsafe virus by using very small parts of the unsafe virus (e.g. only the spike protein) but this safe mRNA payload will “reproduce” inside our cells creating a lot of spike protein. They create a large enough “viral load” to trigger immune response.
There is no body without mRNA and there are basically no viruses that don’t leverage mRNA and therefore all previous vaccines used mRNA we just didn’t have good technology to use it directly.
I hope this helps clarify that “diluted viral load” is an incorrect oversimplification for old/new vaccine science. To understand “old school” vaccines, you would be better off with “boiled viral load” or “cooked viral load” as the oversimplification.
Attenuated viral vaccines, against measles for example, also hijack body cells to make foreign proteins to trigger immune responses.
> I thought traditional vaccines are about injecting the diluted viral load
Umm,no.
I guess live vaccines are kind of like that, but its still a misleading description, and most "traditional" vaccines aren't live vaccines.
Umm,no.
I guess live vaccines are kind of like that, but its still a misleading description, and most "traditional" vaccines aren't live vaccines.
Your original comment was regarding the immune system, in that vein there is no difference in how it trains itself to recognise the inactive virus versus the spike protein made in the body.
When attempting to counter someone's argument you should point out the falsehoods and the ideologically driven parts of it instead of writing them off as so and walking away. But it's far easier to attack without backing it up than to have to defend a position which has been derived from ignorance and the trusting of those who have a pathological history of fraud and corruption. But of course you don't stop there, you then go as far as to project your own shortcomings onto someone who has posted their genuine concern which means, 'quite frankly', I'm going to have to dissect your argument in the way you should have dissected the person whom you replied to, and, by doing so, lead by example.
First off, no, these vaccines are not like standard vaccines, standard vaccines do not introduce the formation of a pathogenic protein in both quantity and quality to that of the pathogen itself which it is attempting to provide protection against. Standard vaccines also do not hijack cellular functionality to produce these pathogenic proteins in both quantity and quality equivalent to that of the pathogen itself. Secondly, you cannot say the vaccines are this or that compared to anything else as these experimental vaccines are not uniform in either their viability or their consistency as a breakdown of batches from the VAERS data reveals 5% of vaccine batches are responsible for 90% of all adverse reactions across all vaccine manufacturers. And if by efficiency you mean having the cells of sensitive organs expressing an overabundance of pathogenic proteins on their surfaces which induces the immune system to engender cellular damage and oxidative stress leading to apoptosis— all incidences which have been documented by the pathologist Dr. Arne Burkhardt—then you need to reconsider your definition of efficiency. We, even to this day, are still not fully sure of how a spike protein interacts with the human organism and the evidence which has come out over the past year shows that the spike protein can affect human cells in multiple different ways which were not taken into consideration by the vaccine manufacturers. The only difference between the complete viral protein and the vaccinal proteins are the inclusion of prolines which supposedly lock the vaccinal spike protein in a state of prefusion but with 1.2 million adverse reactions recorded in VAERS and 25,000 vaccine-associated deaths it's safe to say the prolines don't work as expected and that the vaccinal spike proteins are just as pathogenic as spike proteins which are expressed by SARS-CoV-2.
But your flaccid argument not only fails medically it also fails legally. Even legally these vaccines fall under a completely different set of laws that prevent compensation to those who have been injured. These experimental vaccines are not being treated in the same fashion as standard vaccines as there is a judicial process available for standard vaccine injury where patients are compensated for a vaccine-induced injury as determined through a court procedure which has an appeal process. Compensation for injury or death from these vaccines are instead subject to the heavily restrictive Countermeasures Injury Compensation Program (CICP) instead of the much more robust National Vaccine Injury Compensation Program (VICP):
https://www.hrsa.gov/cicp/cicp-vicp
There is no judicial process for people injured by Covid-19 vaccines through the CICP as is stated on the HRSA website.
Your entire comment is ignorant and I have only begun to dissect it. But it shows you how two seemingly innocuous sentences can hide an entire underbelly of wrongdoing. Remember, when you point the finger you have several other fingers pointing right back at you.
If you are reading this and are at all interested in what I've written here you can read my full argument against these vaccines and their mandates here where I go into these ideas and many more:
https://pastebin.com/qdLXvGWR
First off, no, these vaccines are not like standard vaccines, standard vaccines do not introduce the formation of a pathogenic protein in both quantity and quality to that of the pathogen itself which it is attempting to provide protection against. Standard vaccines also do not hijack cellular functionality to produce these pathogenic proteins in both quantity and quality equivalent to that of the pathogen itself. Secondly, you cannot say the vaccines are this or that compared to anything else as these experimental vaccines are not uniform in either their viability or their consistency as a breakdown of batches from the VAERS data reveals 5% of vaccine batches are responsible for 90% of all adverse reactions across all vaccine manufacturers. And if by efficiency you mean having the cells of sensitive organs expressing an overabundance of pathogenic proteins on their surfaces which induces the immune system to engender cellular damage and oxidative stress leading to apoptosis— all incidences which have been documented by the pathologist Dr. Arne Burkhardt—then you need to reconsider your definition of efficiency. We, even to this day, are still not fully sure of how a spike protein interacts with the human organism and the evidence which has come out over the past year shows that the spike protein can affect human cells in multiple different ways which were not taken into consideration by the vaccine manufacturers. The only difference between the complete viral protein and the vaccinal proteins are the inclusion of prolines which supposedly lock the vaccinal spike protein in a state of prefusion but with 1.2 million adverse reactions recorded in VAERS and 25,000 vaccine-associated deaths it's safe to say the prolines don't work as expected and that the vaccinal spike proteins are just as pathogenic as spike proteins which are expressed by SARS-CoV-2.
But your flaccid argument not only fails medically it also fails legally. Even legally these vaccines fall under a completely different set of laws that prevent compensation to those who have been injured. These experimental vaccines are not being treated in the same fashion as standard vaccines as there is a judicial process available for standard vaccine injury where patients are compensated for a vaccine-induced injury as determined through a court procedure which has an appeal process. Compensation for injury or death from these vaccines are instead subject to the heavily restrictive Countermeasures Injury Compensation Program (CICP) instead of the much more robust National Vaccine Injury Compensation Program (VICP):
https://www.hrsa.gov/cicp/cicp-vicp
There is no judicial process for people injured by Covid-19 vaccines through the CICP as is stated on the HRSA website.
Your entire comment is ignorant and I have only begun to dissect it. But it shows you how two seemingly innocuous sentences can hide an entire underbelly of wrongdoing. Remember, when you point the finger you have several other fingers pointing right back at you.
If you are reading this and are at all interested in what I've written here you can read my full argument against these vaccines and their mandates here where I go into these ideas and many more:
https://pastebin.com/qdLXvGWR
Unless these diseases are causing a worldwide pandemic, or killing off a catastrophe amount of people, these can be tested like normal and not get fast tracked like the covid vaccine one. Just because covid got waivers due to an emergency, does not mean every vaccine going forward will
>It won't surprise me to hear down the line that something subtle went wrong in a sizeable proportion of injectees, and that maybe we rushed into this without taking the time to gather longer term data.
The immune response drops off relatively quickly hence the need for boosters. If the vaccine was cooking the immune system we would've started to see evidence of that long ago.
The immune response drops off relatively quickly hence the need for boosters. If the vaccine was cooking the immune system we would've started to see evidence of that long ago.
SARS-CoV-2 injects people with rna that induces viral fragment production in human cells. It was always a tradeoff between a small non-reproducing set of viral proteins, a full-blown self-reproducing infection of the entire virus that spreads to others, or an endless series of lockdowns (there apparently isn't a possible world where all the countries coordinate to exterminate covid directly).
No, cells infected with full virus rna produce complete copies of the virus (I'm sure there are mistakes) but they are assembled before they break out of the cells. The covid vaccine exclusively induces production of spike protein, which is thought to be the protein that binds to cell surfaces and allows cell entry. Presumably cells which produce the protein and cells to which the proteins attach are attacked by the recipient's immune system.
The human body is in delicate balance and there's a lot that can go wrong. Medical science unironically has only come so far - we just recently discovered the glymphatic system, and that's orders of magnitude in larger, in scale and energies, than cellular level chemical dynamics. Within and without our cells is a soup of thousands of subtlety interacting compounds which is poorly understood.
The human body is in delicate balance and there's a lot that can go wrong. Medical science unironically has only come so far - we just recently discovered the glymphatic system, and that's orders of magnitude in larger, in scale and energies, than cellular level chemical dynamics. Within and without our cells is a soup of thousands of subtlety interacting compounds which is poorly understood.
The disease itself is inflammatory, no?
What is your typically tend to source?
What is your typically tend to source?