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I think slowly will come the realization that mRNA vaccines aren’t as fast to develop as people thought. Sputnik/AstraZeneca vaccines were released almost at th

by f6v 5y ago

I think slowly will come the realization that mRNA vaccines aren’t as fast to develop as people thought. Sputnik/AstraZeneca vaccines were released almost at the same time as Moderna/Pfizer. Yes, the latter were first commercial mRNA vaccines, but the technology is nevertheless rather mature. I watched a lecture by the people credited with creating mRNA vaccines and it turns out people have been working on the technology for decades. Now, the thing is that you can’t just sequence a virus, do bioinformatics, synthesize mRNA and package it into a nano particle. I mean, you can, but chances are it’s going to fail like the CureVac vaccine. The mRNA that gets packaged needs to be modified (I believe with alternative bases) to achieve desired effect. If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine.

glial 5y ago
> Rather, there would be delta- and omicron-specific vaccine. I think there are -- they just haven't made it through the trials and approval processes yet. These are press releases from Pfizer for whatever it's worth: Omicron: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-initiate-study-evaluate-omicron-based https://www.pfizer.com/news/press-release/press-release-deta... Mentions delta: https://cdn.pfizer.com/pfizercom/2021-07/Delta_Variant_Study_Press_Statement_Final_7.8.21.pdf?IPpR1xZjlwvaUMQ9sRn2FkePcBiRPGqw https://cdn.pfizer.com/pfizercom/2021-07/Delta_Variant_Study...
- f6v 5y ago
  Yes, but what I meant was those would be already approved.
  - copperx 5y ago
    What's the rationale behind your assertion?
  - jsharpe 5y ago
    Regulation will take time to catch up. We manage to create and approve a flu vaccine every year, and that's likely because the general process has been approved, and so each iteration is fast tracked. I don't think that's the case with mRNA vaccines yet.
    - Izkata 5y ago
      The yearly flu shot is composed of preexisting vaccines, they're not developed anew each year.
  - lhoff 5y ago
    I assume that still has something to do with mRNA being a novel vaccine type. Therefore the regulatory bodies are still carefull. If Moderna, Biontech and other potential players show again and again that there process of developing new vaccines is safe, I'd guess the time to market will getting shorter and shorter.
  - LeanderK 5y ago
    you can't do this since you need studies and those take time. Depending in the size of your cohort and the current viral load in the population. Curevacs study had the problem that during this time in germany the corona-virus wasn't that common so nobody knew whether the vaccine is working. As I understood it, the actual vaccine was developed super quickly and then everybody waited for the results of the study.
selectodude 5y ago
The omicron and delta vaccines have existed for awhile now. The FDA requires efficacy testing for each individual booster. If the omicron specific booster isn’t better “enough” than a booster of the already approved vaccine, it’s going to be suck in approval hell. Regulatory bodies need to adjust to the new speed of mRNA vaccine production if we want that sort of release schedule.
vkou 5y ago
> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine. Is this a problem with mRNA, a problem with the approval-for-vaccine-variants process, a problem with funding, or a problem with the politicians who thought COVID would magically go away by August 2021 (Never mind that most of the world was nowhere close to being vaccinated, and the millions of sick people throughout it were happily producing variants)? I am ignorant on most of these subjects, but I would be surprised if the mRNA part of that was the problem!
- f6v 5y ago
  What I’m trying to say is that mRNA vaccines might not be faster to deliver to market because you still need to go though testing and approval.
  - ceejayoz 5y ago
    The annual flu shot indicates there is presumably a "same vaccine, slightly different strain" streamlined procedure that can be used. I'd expect the same to occur with COVID boosters over time.
im3w1l 5y ago
The slow part is the safety testing right? If we had a robust enough theory of vaccines safety we could reduce that. How are the yearly flu shots tested anyway? Now, I would not take such a HIV shot. But for high risk groups, think promiscious homosexuals, it may eventually be worth it.
- f6v 5y ago
  If we had robust enough theory of vaccine testing it wouldn’t matter what kind of vaccine you develop, right?
  - im3w1l 5y ago
    Maybe, maybe not? Mrna vaccines are very customizable so they could be specifically engineered to avoid known safety issues for example.
  - lobocinza 5y ago
    I'm not from a bio-science area but AFAIK mRNA vaccines are robust. 1. The same mechanism of deliver is used so it's already tested and know to be safe/effective. 2. It replicates the same protein(s) found on the virus. So it will not due more damage than getting the virus and it will have a high probability of being effective.
- rzz3 5y ago
  If we can do it this fast and this safely for COVID, we should do the same for this disease.
  - grayfaced 5y ago
    Efficacy trials are quick for a disease with 100k infections a day. It's much slower for something that has that many cases a year. It's much harder to tell a statistical difference from noise when you're talking minuscule cases in trial groups.
- dragonwriter 5y ago
  > The slow part is the safety testing right? No, the slow part is the efficacy testing.
onlyrealcuzzo 5y ago
> Sputnik/AstraZeneca vaccines were released almost at the same time as Moderna/Pfizer Most of the time and cost is associated with the trials - not the actual development AFAIK. What would be more promising is if MRNA proves to be much more likely to pass trials. I think we need a lot more attempts at different viruses to have an idea here. Certainly - if this HIV vaccine /does/ work - that's a huge win for MRNA. > If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine. This is nonsense. The traditional vaccines don't work any better. They're worse. This is evidence MRNA is better than traditional vaccines.
- f6v 5y ago
  > The traditional vaccines don't work any better. Didn’t say they were. Rather that mRNA don’t seem to be approved faster for the new variants. > This is evidence MRNA is better than traditional vaccines. Haven’t been following the field that closely. I only seen one pre-print(probably Hungary?) where Sputnik was on par. Would love to see data if you’re willing to share. Edit: I admit I’m a bit confused since I mixed “traditional vaccines” and Sputnik/AZ together. The latter aren’t traditional since adenovirus-based vaccines haven’t been previously deployed, same as mRNA vaccines.
tialaramex 5y ago
Both the Oxford-AstraZeneca vaccine and Sputnik are using a pretty similar trick that gives them the speed-up. They still get to pick an arbitrary sequence, but they're smuggling it inside a virus instead of as mRNA. That's why the codename for the AstraZeneca vaccine is ChAdOx1, it's a Chimp Adenovirus as host for the sequence. Take this mild uninteresting chimpanzee virus, but tweak it to tell human cells to produce your arbitrary sequence instead of itself. The humans become immune to whatever your sequence was (and maybe to Chimp Adenoviruses?). I'm sure there are reasons this might be better in some cases, and it involved less bleeding edge technology which made it a safer bet in a pandemic, but the mRNA approach seems obviously more general and even perhaps more re-usable.
- dpark 5y ago
  > and maybe to Chimp Adenoviruses Which is a major problem with this technique. One of the other vaccines (J&J?) used a relatively harmless human virus and as I recall, some people with previous exposure had no effect from the vaccine.
  - morpheuskafka 5y ago
    Likewise, it would seem that after one vaccine using a given vector, completely unrelated vaccines using the same vector would be ineffective? So presumably they would eventually run out of all the accessible vectors.
- semerda 5y ago
  I wouldn't call it arbitrary sequence, it's a specific sequence ie. s protein for covid. Saying that, it's now a known cause of blood clotting in some recipients: https://www.science.org/doi/10.1126/sciadv.abl8213 https://www.science.org/doi/10.1126/sciadv.abl8213 "chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 5 (HAd-V-C5) and human adenovirus type 26 (HAdV-D26) — the scientists found that ChAdOx1 had a strong negative charge, which meant that it attracted PF4, which has a positive charge."
- selcuka 5y ago
  > but the mRNA approach seems obviously more general and even perhaps more re-usable We should also see how subunit protein vaccines such as Novavax will perform once they are widely available. From what it looks they should be equally effective and more anti-vaxxer friendly.
lobocinza 5y ago
The way I understand is that that design and manufacturing is the smaller share of the lead time for mRNA and non-mRNA. The pre-clinic and clinic trials along with any regulatory delay take most of the time. Still mRNA vaccines are better and cheaper than conventional vaccines after CAPEX is done. Both Moderna and Pfizer have trials running for Omicron.
SideburnsOfDoom 5y ago
> it turns out people have been working on the (mRNA vaccines) technology for decades. if you mean "Developing mRNA vaccines from nothing to a working product" then yes, that's taken decades. I don't really think that fact has much to say about if when you're already making millions of doses of commercial mRNA vaccines around the world this year, how fast next year's version can be made, tested, approved, manufactured at scale and deployed. The challenges involved seem to non-overlapping. "delta- and omicron-specific vaccines" are coming soon, but this is still the very early days on mRNA vaccines, as a commercial mass-scale product.
outworlder 5y ago
One single employee at Pfizer created 10 vaccine candidates in one day. > Now, the thing is that you can’t just sequence a virus, do bioinformatics, synthesize mRNA and package it into a nano particle. You can, and that's exactly what was done. However, out of the 10 or so candidates, they selected a few of the more promising ones to continue research. They are fast to develop. However, there are other steps in the pipeline that aren't so fast. > The mRNA that gets packaged needs to be modified (I believe with alternative bases) to achieve desired effect. That's the easy part. The full mRNA sequence is not that large (https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...) and many of such substitutions can be done by algorithms. Now, maybe the modified protein won't fold right. That's not as easy (although, we can compute how it will fold now). > If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. If we were reckless and just wanted to inject someone with the latest update, this could be done in a matter of days. Human trials took months and people still complained that it was 'developed too quickly'. Then there's logistics.
- f6v 5y ago
  I think you underestimate the effort needed to create an immunogenic vaccine candidate that doesn’t have unwanted side effects. That’s one of the reasons CureVac failed: https://www.nature.com/articles/d41586-021-01661-0 https://www.nature.com/articles/d41586-021-01661-0 And yes, AlphaFold is a major milestone, but I don’t think we’ve solved protein folding for good.
  - et2o 5y ago
    CureVac did not have any pseudouridine modifications. This is relatively easy to do and I’m not sure why they did not do it.
- selcuka 5y ago
  > If we were reckless and just wanted to inject someone with the latest update, this could be done in a matter of days. Human trials took months and people still complained that it was 'developed too quickly'. Then there's logistics. I'm sure there is also the commercial concerns about cannibalising their own product. Would you take the 1-strain BioNTech vaccine if you knew that a 5-strain is also in circulation?
tiahura 5y ago
I think slowly will come the realization that mRNA vaccines aren’t as fast to develop as people thought. It took 2 days to develop the vaccine. https://nymag.com/intelligencer/amp/2020/12/moderna-covid-19-vaccine-design.html https://nymag.com/intelligencer/amp/2020/12/moderna-covid-19...
lamontcg 5y ago
> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine. There are about 5 different false assertions in here with nothing to back them up. The Israelis have found that a 4th shot isn't particularly useful in immocompetent healthy younger adults under 65. We're unlikely to have a 4th shot. This makes sense because in between the first dose(s) and the booster shot the immune system had time for the response to mature via hypermutation/maturation. There's nothing wrong with the mRNA vaccines either since they're better for this virus than any other vaccine for this virus. The old school inactivate virus vaccines are worse than mRNA vaccines (although cheaper and easier to mass produce). People compare mRNA vaccines to the polio vaccine but that is apples and oranges, since coronavirus is a virus that doesn't typically have a viremic phase (outside of severe multi-organ COVID). An appropriate comparison would be between coronavirus vaccines and flu vaccines. Comparing a coronavirus vaccine to a polio vaccine is just ignorant. The mRNA vaccines are also wildly successful by the measure which matters most, which is protection against severe disease and death. They were never promised as being perfect against contracting the disease and transmission. You can lookup very public headline statements from Fauci in late 2020 before the vaccine trials were done setting expectations around a 50% vaccine efficacy against contracting disease. We're also unlikely to be chasing after reformulating the vaccine for specific variants since by the time it could be updated and a hundred million doses were produced and shipped and we tried to get them into people's arms the variant wave would be over in that region. Just producing and moving the doses is a logistics problem that will take months. And the boosted response to the ancestral virus is still very strong against Omicron, and there's no evidence of any waning of efficacy against severe disease or hospitalization and no evidence of escape from T-cells (and the pattern of mutations in Omicron is random with respect to T-cell epitopes and shows no clustering). The newspapers never should have sold vaccines as a way to stop the virus in its tracks. That isn't a problem with the science or the technology though. That is just that human emotions got out of control wishing for a magic shot that would make it all stop. People often complain about the trials being cut short, but in fact we had enough data to determine the efficacy and safety outcomes. What we cut short was durability. Turns out the neutralizing antibodies and efficacy against infection/disease wane over 6-12 months (as it does with natural infection as well). That's the reason why the original 90% VE against infection numbers turned out to be wrong, we cut the studies short to start getting it into arms. The 90% VE against hospitalization/death have been maintained though.
CorrectHorseBat 5y ago
As I understand it delta boosters have been tested, but were not more effective than a normal booster. Omicron has only been discovered in November and booster trials are still ongoing.

by f6v 5y ago

glial 5y ago

> Rather, there would be delta- and omicron-specific vaccine. I think there are -- they just haven't made it through the trials and approval processes yet. These are press releases from Pfizer for whatever it's worth: Omicron: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-initiate-study-evaluate-omicron-based https://www.pfizer.com/news/press-release/press-release-deta... Mentions delta: https://cdn.pfizer.com/pfizercom/2021-07/Delta_Variant_Study_Press_Statement_Final_7.8.21.pdf?IPpR1xZjlwvaUMQ9sRn2FkePcBiRPGqw https://cdn.pfizer.com/pfizercom/2021-07/Delta_Variant_Study...

f6v 5y ago
Yes, but what I meant was those would be already approved.
- copperx 5y ago
  What's the rationale behind your assertion?
- jsharpe 5y ago
  Regulation will take time to catch up. We manage to create and approve a flu vaccine every year, and that's likely because the general process has been approved, and so each iteration is fast tracked. I don't think that's the case with mRNA vaccines yet.
  - Izkata 5y ago
    The yearly flu shot is composed of preexisting vaccines, they're not developed anew each year.
- lhoff 5y ago
  I assume that still has something to do with mRNA being a novel vaccine type. Therefore the regulatory bodies are still carefull. If Moderna, Biontech and other potential players show again and again that there process of developing new vaccines is safe, I'd guess the time to market will getting shorter and shorter.
- LeanderK 5y ago
  you can't do this since you need studies and those take time. Depending in the size of your cohort and the current viral load in the population. Curevacs study had the problem that during this time in germany the corona-virus wasn't that common so nobody knew whether the vaccine is working. As I understood it, the actual vaccine was developed super quickly and then everybody waited for the results of the study.

selectodude 5y ago

The omicron and delta vaccines have existed for awhile now. The FDA requires efficacy testing for each individual booster. If the omicron specific booster isn’t better “enough” than a booster of the already approved vaccine, it’s going to be suck in approval hell. Regulatory bodies need to adjust to the new speed of mRNA vaccine production if we want that sort of release schedule.

vkou 5y ago

> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine. Is this a problem with mRNA, a problem with the approval-for-vaccine-variants process, a problem with funding, or a problem with the politicians who thought COVID would magically go away by August 2021 (Never mind that most of the world was nowhere close to being vaccinated, and the millions of sick people throughout it were happily producing variants)? I am ignorant on most of these subjects, but I would be surprised if the mRNA part of that was the problem!

f6v 5y ago
What I’m trying to say is that mRNA vaccines might not be faster to deliver to market because you still need to go though testing and approval.
- ceejayoz 5y ago
  The annual flu shot indicates there is presumably a "same vaccine, slightly different strain" streamlined procedure that can be used. I'd expect the same to occur with COVID boosters over time.

im3w1l 5y ago

The slow part is the safety testing right? If we had a robust enough theory of vaccines safety we could reduce that. How are the yearly flu shots tested anyway? Now, I would not take such a HIV shot. But for high risk groups, think promiscious homosexuals, it may eventually be worth it.

f6v 5y ago
If we had robust enough theory of vaccine testing it wouldn’t matter what kind of vaccine you develop, right?
- im3w1l 5y ago
  Maybe, maybe not? Mrna vaccines are very customizable so they could be specifically engineered to avoid known safety issues for example.
- lobocinza 5y ago
  I'm not from a bio-science area but AFAIK mRNA vaccines are robust. 1. The same mechanism of deliver is used so it's already tested and know to be safe/effective. 2. It replicates the same protein(s) found on the virus. So it will not due more damage than getting the virus and it will have a high probability of being effective.
rzz3 5y ago
If we can do it this fast and this safely for COVID, we should do the same for this disease.
- grayfaced 5y ago
  Efficacy trials are quick for a disease with 100k infections a day. It's much slower for something that has that many cases a year. It's much harder to tell a statistical difference from noise when you're talking minuscule cases in trial groups.
dragonwriter 5y ago
> The slow part is the safety testing right? No, the slow part is the efficacy testing.

onlyrealcuzzo 5y ago

> Sputnik/AstraZeneca vaccines were released almost at the same time as Moderna/Pfizer Most of the time and cost is associated with the trials - not the actual development AFAIK. What would be more promising is if MRNA proves to be much more likely to pass trials. I think we need a lot more attempts at different viruses to have an idea here. Certainly - if this HIV vaccine /does/ work - that's a huge win for MRNA. > If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine. This is nonsense. The traditional vaccines don't work any better. They're worse. This is evidence MRNA is better than traditional vaccines.

f6v 5y ago
> The traditional vaccines don't work any better. Didn’t say they were. Rather that mRNA don’t seem to be approved faster for the new variants. > This is evidence MRNA is better than traditional vaccines. Haven’t been following the field that closely. I only seen one pre-print(probably Hungary?) where Sputnik was on par. Would love to see data if you’re willing to share. Edit: I admit I’m a bit confused since I mixed “traditional vaccines” and Sputnik/AZ together. The latter aren’t traditional since adenovirus-based vaccines haven’t been previously deployed, same as mRNA vaccines.

tialaramex 5y ago

Both the Oxford-AstraZeneca vaccine and Sputnik are using a pretty similar trick that gives them the speed-up. They still get to pick an arbitrary sequence, but they're smuggling it inside a virus instead of as mRNA. That's why the codename for the AstraZeneca vaccine is ChAdOx1, it's a Chimp Adenovirus as host for the sequence. Take this mild uninteresting chimpanzee virus, but tweak it to tell human cells to produce your arbitrary sequence instead of itself. The humans become immune to whatever your sequence was (and maybe to Chimp Adenoviruses?). I'm sure there are reasons this might be better in some cases, and it involved less bleeding edge technology which made it a safer bet in a pandemic, but the mRNA approach seems obviously more general and even perhaps more re-usable.

dpark 5y ago
> and maybe to Chimp Adenoviruses Which is a major problem with this technique. One of the other vaccines (J&J?) used a relatively harmless human virus and as I recall, some people with previous exposure had no effect from the vaccine.
- morpheuskafka 5y ago
  Likewise, it would seem that after one vaccine using a given vector, completely unrelated vaccines using the same vector would be ineffective? So presumably they would eventually run out of all the accessible vectors.
semerda 5y ago
I wouldn't call it arbitrary sequence, it's a specific sequence ie. s protein for covid. Saying that, it's now a known cause of blood clotting in some recipients: https://www.science.org/doi/10.1126/sciadv.abl8213 https://www.science.org/doi/10.1126/sciadv.abl8213 "chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 5 (HAd-V-C5) and human adenovirus type 26 (HAdV-D26) — the scientists found that ChAdOx1 had a strong negative charge, which meant that it attracted PF4, which has a positive charge."
selcuka 5y ago
> but the mRNA approach seems obviously more general and even perhaps more re-usable We should also see how subunit protein vaccines such as Novavax will perform once they are widely available. From what it looks they should be equally effective and more anti-vaxxer friendly.

lobocinza 5y ago

The way I understand is that that design and manufacturing is the smaller share of the lead time for mRNA and non-mRNA. The pre-clinic and clinic trials along with any regulatory delay take most of the time. Still mRNA vaccines are better and cheaper than conventional vaccines after CAPEX is done. Both Moderna and Pfizer have trials running for Omicron.

SideburnsOfDoom 5y ago

> it turns out people have been working on the (mRNA vaccines) technology for decades. if you mean "Developing mRNA vaccines from nothing to a working product" then yes, that's taken decades. I don't really think that fact has much to say about if when you're already making millions of doses of commercial mRNA vaccines around the world this year, how fast next year's version can be made, tested, approved, manufactured at scale and deployed. The challenges involved seem to non-overlapping. "delta- and omicron-specific vaccines" are coming soon, but this is still the very early days on mRNA vaccines, as a commercial mass-scale product.

outworlder 5y ago

One single employee at Pfizer created 10 vaccine candidates in one day. > Now, the thing is that you can’t just sequence a virus, do bioinformatics, synthesize mRNA and package it into a nano particle. You can, and that's exactly what was done. However, out of the 10 or so candidates, they selected a few of the more promising ones to continue research. They are fast to develop. However, there are other steps in the pipeline that aren't so fast. > The mRNA that gets packaged needs to be modified (I believe with alternative bases) to achieve desired effect. That's the easy part. The full mRNA sequence is not that large (https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...) and many of such substitutions can be done by algorithms. Now, maybe the modified protein won't fold right. That's not as easy (although, we can compute how it will fold now). > If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. If we were reckless and just wanted to inject someone with the latest update, this could be done in a matter of days. Human trials took months and people still complained that it was 'developed too quickly'. Then there's logistics.

f6v 5y ago
I think you underestimate the effort needed to create an immunogenic vaccine candidate that doesn’t have unwanted side effects. That’s one of the reasons CureVac failed: https://www.nature.com/articles/d41586-021-01661-0 https://www.nature.com/articles/d41586-021-01661-0 And yes, AlphaFold is a major milestone, but I don’t think we’ve solved protein folding for good.
- et2o 5y ago
  CureVac did not have any pseudouridine modifications. This is relatively easy to do and I’m not sure why they did not do it.
selcuka 5y ago
> If we were reckless and just wanted to inject someone with the latest update, this could be done in a matter of days. Human trials took months and people still complained that it was 'developed too quickly'. Then there's logistics. I'm sure there is also the commercial concerns about cannibalising their own product. Would you take the 1-strain BioNTech vaccine if you knew that a 5-strain is also in circulation?

tiahura 5y ago

I think slowly will come the realization that mRNA vaccines aren’t as fast to develop as people thought. It took 2 days to develop the vaccine. https://nymag.com/intelligencer/amp/2020/12/moderna-covid-19-vaccine-design.html https://nymag.com/intelligencer/amp/2020/12/moderna-covid-19...

lamontcg 5y ago

> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine. There are about 5 different false assertions in here with nothing to back them up. The Israelis have found that a 4th shot isn't particularly useful in immocompetent healthy younger adults under 65. We're unlikely to have a 4th shot. This makes sense because in between the first dose(s) and the booster shot the immune system had time for the response to mature via hypermutation/maturation. There's nothing wrong with the mRNA vaccines either since they're better for this virus than any other vaccine for this virus. The old school inactivate virus vaccines are worse than mRNA vaccines (although cheaper and easier to mass produce). People compare mRNA vaccines to the polio vaccine but that is apples and oranges, since coronavirus is a virus that doesn't typically have a viremic phase (outside of severe multi-organ COVID). An appropriate comparison would be between coronavirus vaccines and flu vaccines. Comparing a coronavirus vaccine to a polio vaccine is just ignorant. The mRNA vaccines are also wildly successful by the measure which matters most, which is protection against severe disease and death. They were never promised as being perfect against contracting the disease and transmission. You can lookup very public headline statements from Fauci in late 2020 before the vaccine trials were done setting expectations around a 50% vaccine efficacy against contracting disease. We're also unlikely to be chasing after reformulating the vaccine for specific variants since by the time it could be updated and a hundred million doses were produced and shipped and we tried to get them into people's arms the variant wave would be over in that region. Just producing and moving the doses is a logistics problem that will take months. And the boosted response to the ancestral virus is still very strong against Omicron, and there's no evidence of any waning of efficacy against severe disease or hospitalization and no evidence of escape from T-cells (and the pattern of mutations in Omicron is random with respect to T-cell epitopes and shows no clustering). The newspapers never should have sold vaccines as a way to stop the virus in its tracks. That isn't a problem with the science or the technology though. That is just that human emotions got out of control wishing for a magic shot that would make it all stop. People often complain about the trials being cut short, but in fact we had enough data to determine the efficacy and safety outcomes. What we cut short was durability. Turns out the neutralizing antibodies and efficacy against infection/disease wane over 6-12 months (as it does with natural infection as well). That's the reason why the original 90% VE against infection numbers turned out to be wrong, we cut the studies short to start getting it into arms. The 90% VE against hospitalization/death have been maintained though.

CorrectHorseBat 5y ago

As I understand it delta boosters have been tested, but were not more effective than a normal booster. Omicron has only been discovered in November and booster trials are still ongoing.