If you read the trial data this is a foregone conclusion. The Moderna vaccine produces antibody titres over twice as high as an actual infection from the data I've seen.
My theory is that these companies knew they only had one chance to make a working vaccine, so they did everything they could to make it not fail. Double doses, 5x what was needed in monkeys, gold standard adjuvants.
I would not be amazed in the slightest if they decide to half-dose the vaccine or do away with the second shot or even both. They probably didn't have time to run the trial any other way
If you look at some of their published Phase 2 data, they were actually getting good responses from their 25mcg dosing. But you're correct--this was the fastest vaccine development in the history of mankind, and they errored on doing the 100mcg version just to make sure the efficacy was high enough because they didn't have time to test it on a wider population or do challenge trials.
Imagine the blowback on mRNA vaccines in general if they went with the low-dose version and got lowered efficacy...
However, I found it interesting that the vaccine seems to possibly even work somewhat against SARS-1 and MERS, which inspires a lot of hope that the vaccines could be at least partially protective against future variants.
It is unfortunate. You can't even avoid downvotes in a fairly rational place like HN :) .
I've been following the vaccine development pretty closely and everything looks like a "this can't fail" mentality.
People need to realize that it's rational to ask if we really need the dose this high and really need a booster because if we find out we don't, it could double or even quadruple our vaccine supply. That could save half a million lives.
It's good to ask questions like this especially when there's a massive worldwide vaccine shortage
Without specifically criticizing this vaccine process, I would add that if you start digging into medical research, you will find this is the rule rather than the exception. I've had my own semi-obscure issues I've gone trolling through the literature for assistance with, and one of the things I've found is that you'll find something that is tested; for a specific example, I found some examination of taurine supplementation for heart arrhythmia issues. There were multiple papers that all studied the exact same dosing schedule. This strongly suggests to me that the initial schedule was basically someone thinking for a moment and giving an informed guess about what might work.
This is just an observation, not a criticism, because I don't have a better suggestion for what they can do, nor do I particularly believe there is a much better suggestion necessarily. You have to start somewhere. My point is just that you shouldn't overestimate the exact numbers and how much effort was put into exploring all the details. Obviously some things are deeply studied, but most things won't be.
This implies that, statistically speaking, there very likely are drugs that were formulated, created, and put into a testing regime that they failed that actually work great, but were just dosed out to the study participants such that the good effects didn't emerge yet, or were dosed on a poor schedule, etc. (Or would have worked great if paired with a hit of grapefruit. [1]) I also wonder how that compares to the number of drugs that were never tested on humans because they failed animal testing, but it turns out that in reality they would have been fine in humans. Just idle musings on life.
Well, these are the numbers we have and which have been confirmed by the proper trials. I am sure, there is more research getting performed to optimize the vaccines, but we fortunately can vaccinate with good results based on these numbers.
They should be sacred until we have completed studies with other regimens. What we have is a theory but we need to collect data to correctly identify the best timing.
Interesting, I hadn't known that. I imagine the short booster dose time also helps in implementation, because an individual gets maximum immunity 6 weeks after the first dose (4 weeks pause + 2 weeks) rather than 28 weeks (6 month pause + 2 weeks) for a longer pause. Having a longer pause to maximize individual immunity might not be the fastest way to maximize population immunity during an ongoing pandemic.
I think the mRNA vaccines don't contain any adjuvants at all. They are so awesome, because they are comparatively simple systems.
I would choose the mRNA vaccines over adenovirus-based ones, because of that. Drive-by immunity to the adenovirus carriers could render future vaccines useless, when there is no alternative vaccine technology available *. I hope when it's my turn, I will have a choice.
* Edit: My guessing. I am no medical professional, or researcher in a related field. Maybe my worries are completely unsubstantiated. I am also of the "worrying type" https://www.youtube.com/watch?v=pUDv3h09VBc
There's not an added adjuvant in either of the mRNA vaccines. The lipid nanoparticles may be acting as one though (in addition to ferrying the mRNA into cells).
There's no adjuvants being used at all with mRNA vaccines.
Also, there were smaller sub-trials done with just one shot, and those showed significantly weaker immunization, although telling exactly how much weaker is hard due to little data available and thus very large margins of error.
Polyethylene glycol is an adjuvant, as are many of the lipids chosen. It's looking like PEG is maybe a bit too effective at getting the immune system's attention, and that's why we're getting so much anaphylaxis.
We know that both the Moderna and Pfizer vaccines look about 80% effective from 10 days after dose 1 up to dose 2. We really should be doing a trial on delaying dose 2 a bit: it might very well make the dose 2 side effects smaller, increase efficacy, and stretch vaccine supplies.
No traditional adjuvants is interesting, but I know the RNA is modified. It's not the exact mRNA spike protein. I believe they modify the amino acids to modulate immune reaction which may accomplish the same thing.
The immune system doesn't like non-human RNA. Certain sequences, or even abundance of certain amino acids out of balance with human codes can set it off. Special RNA coding may be used in place of traditional adjuvants but much of it is proprietary at this point
There is a conceptual misunderstanding here. Raising the dose doesn't mean you have a higher efficacy, in fact it can just as easily have the reverse effect. Vaccines aren't beer where you consume twice as much and get twice as drunk.
Granted. But there is a minimum dose necessary to produce antibodies. If you are in a situation where you are guessing completely blindly (because no trial like yours has been done before), do you worry more about falling below the minimum required dose or above the maximum dose past which you get diminishing returns or even lower efficacy? I think it’s reasonable to worry more about the minimum dose because you can always half the doses later. Finding out at the end of a multi-month trial that you didn’t give enough in your doses would be a big setback. Just look at what happened with Assyria Zeneca when they started mixing up dosing in their phase III. They were the most promising vaccine last summer and they haven’t even concluded their US phase III trial yet as a result.
I mean technically an alcohol could exist that makes you less drunk after twice as much but how likely is that? IMO about as likely as a vaccine that produces less immunity with higher dosage
Neither Pfizer-BioNTech or Moderna's vaccines bring any additional adjuvants to the yard. mRNA is inherently immunogenic. This speaks generally about mRNA vaccines and touches on that property, among others: https://www.cell.com/trends/molecular-medicine/fulltext/S147...
Coming from Israel,
What I'm writing is about Pfizer but related to the article above.
Since the Pfizer vaccine is much more complex to maintain. Once you unfreeze it, there's a time window for it to be usable.
In addition to many other factors "modified" by the Israeli HMO, an interesting one related to the above is the allowance of an extra dose from each bottle. The Pfizer bottle were tested as 5 dozes per bottle.
The HMO here allowed 6 dozes.
I'm not a molecular biologist or medical experimental. But that sounds a bit bad medical testing. To just increase the dosage like this with out proper longitudinal studies. Anyone with that area of expertise care of pitch in here?
The studies will eventually come out with "proper longitudinal studies". Some countries are choosing not to wait for that. I do hope they do those studies - it feels like half the current dose size might work fine
So many people in the comments are just certain that more money wouldn't have made any difference to vaccine production, and that economic considerations had nothing to do with it. The arguments they make fail to simple comparison tests:
"If we paid Tesla 2x as much per car, could they really not produce more cars?"
They also fail to privileging the status quo - "If we paid Tesla half as much money, would they produce fewer cars?"
Obviously, they would. Money influences how easily they can produce cars. At the margin there must be decisions related to turning money into efficiency every day. And the same thing must apply for vaccines. The best vaccine expert in the world asked for a yearly sabbatical - 200k wasn't enough to keep them. Double that to 400k? Oh actually it can wait til next year.
The question for people who deny money's ability to produce more vaccines is: why do you admit that any lower price for a vaccine would reduce supply - but you deny that any higher price would increase supply. What magic is this?
From what I understand, the problem with scaling the Moderna/Pfizer vaccines is that they use a novel process that hasn't been used for producing a vaccine at scale previously. They're having to build out entirely new factories and supply chains. This sort of work normally takes years.
Would throwing more money at the problem ease some bottlenecks in increasing production? maybe? Would it cut months off the time to complete the roll out? Plausibly. However, I don't think it'd make a huge difference to the speed of the roll out over the next six months or so. Some things just take time to ramp up.
> They also fail to privileging the status quo - "If we paid Tesla half as much money, would they produce fewer cars?"
They would quite certainly produce no car at all - the economics would not work out. But Teslas, and vaccines, are being produced, so you analogy seems pointless.
Right. So continue your reasoning: you are arguing that if we pay the minimum required to produce an item, from that point onwards, more money doesn't unlock additional production? I agree you need to be able to charge enough to cover costs; the question is what happens after that. Why does it require proof to suggest that paying someone slightly more than the absolute minimum they'd ask to do something will increase their willingness and ability to do it?
At 20/dose, companies could produce N. At 30/dose they could probably find a way to produce more (perhaps by spending money to retrofit an old machine, which at 20/dose wouldn't have been worth it). And at 100/dose they can afford to fly the device manufacturer out to personally oversee sped-up installation.
Money works well to speed things up until your project hits the the grindingly slow beast known as the federal bureaucracy. Then money potentially still works, but in ways that produce many negative externalities.
They've probably underpriced vaccine really. I guess we're spending $5-$40 per head and the value to the economy of getting back to normal a couple of months earlier is likely over $1000.
More money per dose might have increased the efforts of the vaccine producers to speed up production and given them more financial means to do so. However, this still would not have been the optimal solution.
This is a case, where governments should have directly funded the build-up of production capacity. We need production capacities at a level which is economically infeasibly from a vendors perspective. Internationally, we need to produce like 14 billion doses per year. This would mean that whole humanity could be vaccinated within a year. Which is what we need, if we want to erradicate Sars-cov-2. But if we manage to do that, most of those new plants would become redundant and thats exactly why the government needs to pay for them.
What I don't get is why the EU doesn't buy the vaccine patents from e.g. Pfizer (or failing that, buy Pfizer outright - it would still only cost a fraction of what the lockdowns and aid packages have cost) and release the patents into public domain, so all companies with the capability can produce the vaccine. If it could hasten the reopenings by just one month, it would still be a terrific ROI.
The results in Figure 3 are certainly promising. Has anyone been able to find the mentioned supplementary material though?
> A post-hoc exploratory analysis of immunogenicity in subgroups of participants aged ≥55-<65, ≥65-74 and ≥75 years was performed (Tables S6 and S7). Increases in levels of anti-SARS-CoV-2-spike bAb and nAb at days 29 and post-second vaccination at both the 50 and 100 ug doses were generally comparable across the age subgroups and with those observed in the younger (18-55 years) study participants. Seroconversion rates were also comparable across the age groups and with those in the younger participants. It should be noted that the small size of the ≥75 year-old subgroup (n=22) precludes definitive conclusions to be made.
There doesn't seem to be any link to supplementary material at either the Elsevier page [1] nor the NIH page [2]. The clinical trial registration [3] suggests that there was an update just a few days ago, so perhaps they're just waiting to upload a new PDF?
Probably not available as part of the journal's "pre-proof" process. You'll likely have to wait until the formal publication date.
> These versions will undergo additional copyediting, typesetting and review, and may not yet have full ScienceDirect functionality. For example, supplementary files may still need to be added, links to references may not resolve yet, etc. The text could still change before final publication.
(Summarizing things I've picked up from reading Derek Lowe's blog [0])
Not all antibodies are neutralizing. Antibodies can only bind to a certain part of pathogens, but if an antibody binds to something it might not disrupt what that thing needs to do to infect the body. Relating this to SARS-CoV-2, it looks like if an antibody bind to something other than the spike protein, the virus can still infect cells. As another example, most people have been exposed to at least some other coronaviruses, and of that group, some of those people have developed antibodies that react to SARS-CoV-2. A recent paper [1] looked at if these "cross-reactive" antibodies were helpful in preventing COVID, but it looks like they're non-neutralizing as they couldn't see any effect.
The Moderna dose is already more than 3x the dosage of the Pfizer ones. 100mcg vs 30mcg. Would be great if they could cut that down and still be effective.
They're not the same formulation, so you can't compare the dosing, it's Apples vs. Walnuts
The problem with the 50mcg dose is that there is justifiable concern that if you error on the side of low-dosing that the mass vaccination won't work and the public sentiment will turn against it. We'd rather see 95% efficacy with the 100mcg than risk the POSSIBILITY of 60% efficacy with the 50mcg dose. We literally have one shot (or two, pun intended) to get it right the first time. Only 4 months ago, most of the world hadn't even heard of mRNA vaccines or somehow believed it was micro-chipped by Bill Gates. Much of that nonsense has gone away because they're getting unbelievable efficacy that's higher than the traditionally-made vaccines from Astra-Zeneca and JnJ.
Yeah. And a dose of vitamin C at 3000 mg is 30,000 larger than Moderna’s. You are comparing apples and cheese. Simply weighing them won’t tell you anything.
I gotta say that the dose really is a pain in the arm. We ended up on the list at work and the first dose hurt for a good four days. Others had a similar outcome. My father got the first Pfizer and he reported no issues with his arm hurting. I doubt he was not telling the truth on that one.
So... if that plays out, perhaps split the doses in half, cover twice the people, so we can all go back to our normal pre-COVID life (or what's left of it).
Of course this won't double the number of people vaccinated since Moderna doesn't cover 100%. But every little helps.
We're not going back to pre covid lives period. Even if everyone was vaxxed there would still be more moderate cases that our hospitals can handle. And then that allows the virus millions of chances to mutate and then, just like we're seeing with the UK and South Africa strains. Which as we're seeing all but nullifies the vaccine. The vaccines we're seeing are only 10% effective against the SA strain. Statistically >5% is great, but that's not a risk the vast majority of people want to run with.
I'm surprised some poorer nations haven't taken their ~million vaccine doses, split each one into 20 fractional-doses and inoculated 20 million people.
Sure, the vaccine efficiency probably drops from 93% to 15%, but it's still better to have a population of 15% resistant people than a population where 1 million get 93% protection and 19 million get 0%.
As more doses come in, the country can similarly divide them and give them as 2nd, 3rd and 4th 'boosters'. They'd probably get up to herd immunity levels with far less total vaccine...
I wonder if perhaps the contracts with vaccine producers stop them doing this? (since it might hurt the vaccines reputation)
My understanding is that insufficient dosing could theoretically breed vaccine-resistant variants of the virus, but there's not a lot of data on this, so it's not known how great a risk it is.
One of the many problems in poorer nations is the cost to get people to the vaccination centers. Multiplying that cost 3-4 times does not help.I don't know if mobile vaccination teams are really possible for Moderna and Pfizer, due to temperature requirements.
I wonder if they, like Pfizer, will take the opportunity to declare that they have shipped 2x as many doses retroactively (in Pfizer’s case it was an extra dose in every vial).
Do you have any source or proof regarding that "retroactively" claim?
Because AFAIK they only started to bill customers for 6 doses per vial when they received official regulatory approval for the 6th dose. Vials delivered earlier were not affected, so any 6th dose gathered from them was effectively free.
You are correct, it was not applied retroactively:
> Gottlieb, the former head of the FDA, clarified that the change is not going to be applied retroactively, meaning that all vials previously shipped out are counted as containing five doses.
You seem to imply that that's somehow a trick or a bad thing, but the only valid purpose to counting number of vaccines shipped[1] is as a proxy for the number of vaccines delivered. The extra doses in a vial were a happy accident, not a trick. And the number we actually want to know is the one we're being given now.
If a vaccine vial was shipped in December and was given wholly to one person, that’s one dose. You can’t claim it was two back then because it couldn’t have been used as two.
The real problem I see is that we count vaccine doses as one shot. For Pfizer and Moderna two shots = one dose. It is misleading to show a two vial dose as two doses.
Hundreds of millions of people would pay 5x the current price to get the vaccine faster. I feel like the policy of governments getting a monopoly on vaccine distribution is stopping companies in competing for speed of vaccine production and building more factories.
No, that's preposterous, paying 5x more won't increase production capacity any more.
There's already massive incentive to ship first, since there are competing vaccines. If an additional $10B-$100B could result in additional production of mRNA vaccine, it would have been delivered by governments if not by investors.
This is simply a new tech with new techniques. Throwing extra money at a problem when there isn't a chance of increasing production capacity only causes inflation of prices, and rentierism. There is no benefit.
The ability for companies to charge what they want for the vaccine would ensure only those that could afford it would receive it, and there wouldn't be additional capital investment because that would dilute profits.
In the case of mRNA vaccines, according to what I've read the limiting factor is that they depend on specialized precursors that very few companies can make.
Before the COVID-19 mRNA vaccine all mRNA vaccines that had been developed for humans didn't make it past testing. There was no need to have the ability to make them beyond what was needed for research and testing.
And if one of the prior human mRNA vaccines had looked good in the middle of the phase III trial, the low manufacturing capacity would not have mattered. A normal phase III trial takes years, and the diseases the vaccines were for were not pandemics. So even if it takes a couple years to get up to the needed capacity, that would be fast enough.
With COVID-19 mRNA vaccines, we've got (1) an emergency use authorization rather than a normal approval, so a much shorter time between finding out that the thing works and the start of consumer distribution, and (2) it's a pandemic so the number of doses needed is very very high. That's the worst possible combination.
Please do not bring the American healthcare mentality to a product that is needed by literally everyone. The minute people can spend 5x to get the vaccine means that people will need to spend 5x to get the vaccine.
There's absolutely no evidence that this is the case. Money can't buy things instantly, the vaccine ramp is progressing very well as it is, and if you want to claim that a giant check would somehow produce more shots in arms you need to make that case with data. There are only so many units of the nanolipid production equipment available, and only so many factories that can make more, and only so many engineers who know how to operate those factories.
If this were purely a logistics problem then I would sort of agree with this, at least in the sense of being an avenue worth trying - but as far as I can tell the current problems with the vaccine are mainly in the nitty-gritty details of actually making it in the first place. Right now the companies doing that can basically write their price.
There aren't many people with the expertise to produce the vaccine, and they're all already working on the existing production lines. The lead times are just inherently long here; takes months to start up a production line.
I would normally argue this case, but "factories" is sort of hand-wavy here. The factories dumping out the feedstock are all producing enough to meet a higher level of production. The mixing step is the bottle neck, and is a really hard, expensive process to scale up. Demand for the vaccine is likely to dry up in a year or two, and companies don't want to drastically over shoot building out expensive single purpose tooling.
Is there any evidence that paying 5x the price would actually result in a faster rollout of the vaccine? At a certain scale and timeline you can't throw money at the problem anymore there's a finite limit to how fast our global infrastructure can operate.
Yeah but for that reason I’m very thankful that the government DOES have a monopoly on this process. That’ll ensure the vaccine goes to the people that need it the most first, not just the people that can be gouged the most.
Readit News
My theory is that these companies knew they only had one chance to make a working vaccine, so they did everything they could to make it not fail. Double doses, 5x what was needed in monkeys, gold standard adjuvants.
I would not be amazed in the slightest if they decide to half-dose the vaccine or do away with the second shot or even both. They probably didn't have time to run the trial any other way
Imagine the blowback on mRNA vaccines in general if they went with the low-dose version and got lowered efficacy...
Nope. There's data indicating we must have the second shot for T-cell response, or the vaccine will fail against mutations:
https://www.researchsquare.com/article/rs-226857/v1https://twitter.com/dvir_a/status/1359603522581454856 (done on the Pfizer vaccine, but it's very similar to Moderna)
However, I found it interesting that the vaccine seems to possibly even work somewhat against SARS-1 and MERS, which inspires a lot of hope that the vaccines could be at least partially protective against future variants.
Good job, Pfizer (and Moderna)!
Usually you have a longer pause, which gives somewhat better results.
Now those numbers are treated as sacred by so many.
I've been following the vaccine development pretty closely and everything looks like a "this can't fail" mentality.
People need to realize that it's rational to ask if we really need the dose this high and really need a booster because if we find out we don't, it could double or even quadruple our vaccine supply. That could save half a million lives.
It's good to ask questions like this especially when there's a massive worldwide vaccine shortage
This is just an observation, not a criticism, because I don't have a better suggestion for what they can do, nor do I particularly believe there is a much better suggestion necessarily. You have to start somewhere. My point is just that you shouldn't overestimate the exact numbers and how much effort was put into exploring all the details. Obviously some things are deeply studied, but most things won't be.
This implies that, statistically speaking, there very likely are drugs that were formulated, created, and put into a testing regime that they failed that actually work great, but were just dosed out to the study participants such that the good effects didn't emerge yet, or were dosed on a poor schedule, etc. (Or would have worked great if paired with a hit of grapefruit. [1]) I also wonder how that compares to the number of drugs that were never tested on humans because they failed animal testing, but it turns out that in reality they would have been fine in humans. Just idle musings on life.
[1]: https://news.ycombinator.com/item?id=24705855
I think the mRNA vaccines don't contain any adjuvants at all. They are so awesome, because they are comparatively simple systems.
I would choose the mRNA vaccines over adenovirus-based ones, because of that. Drive-by immunity to the adenovirus carriers could render future vaccines useless, when there is no alternative vaccine technology available *. I hope when it's my turn, I will have a choice.
* Edit: My guessing. I am no medical professional, or researcher in a related field. Maybe my worries are completely unsubstantiated. I am also of the "worrying type" https://www.youtube.com/watch?v=pUDv3h09VBc
Also, there were smaller sub-trials done with just one shot, and those showed significantly weaker immunization, although telling exactly how much weaker is hard due to little data available and thus very large margins of error.
We know that both the Moderna and Pfizer vaccines look about 80% effective from 10 days after dose 1 up to dose 2. We really should be doing a trial on delaying dose 2 a bit: it might very well make the dose 2 side effects smaller, increase efficacy, and stretch vaccine supplies.
The immune system doesn't like non-human RNA. Certain sequences, or even abundance of certain amino acids out of balance with human codes can set it off. Special RNA coding may be used in place of traditional adjuvants but much of it is proprietary at this point
Neither Pfizer-BioNTech or Moderna's vaccines bring any additional adjuvants to the yard. mRNA is inherently immunogenic. This speaks generally about mRNA vaccines and touches on that property, among others: https://www.cell.com/trends/molecular-medicine/fulltext/S147...
Since the Pfizer vaccine is much more complex to maintain. Once you unfreeze it, there's a time window for it to be usable.
In addition to many other factors "modified" by the Israeli HMO, an interesting one related to the above is the allowance of an extra dose from each bottle. The Pfizer bottle were tested as 5 dozes per bottle. The HMO here allowed 6 dozes.
I'm not a molecular biologist or medical experimental. But that sounds a bit bad medical testing. To just increase the dosage like this with out proper longitudinal studies. Anyone with that area of expertise care of pitch in here?
Dead Comment
My understanding is the mRNA based vaccines already aren’t as effective at long-term protection. But happy to be corrected if someone had insight.
Source? I've never seen anything that suggests that, and can't even think of a rationale why it would ever be true?
"If we paid Tesla 2x as much per car, could they really not produce more cars?"
They also fail to privileging the status quo - "If we paid Tesla half as much money, would they produce fewer cars?"
Obviously, they would. Money influences how easily they can produce cars. At the margin there must be decisions related to turning money into efficiency every day. And the same thing must apply for vaccines. The best vaccine expert in the world asked for a yearly sabbatical - 200k wasn't enough to keep them. Double that to 400k? Oh actually it can wait til next year.
The question for people who deny money's ability to produce more vaccines is: why do you admit that any lower price for a vaccine would reduce supply - but you deny that any higher price would increase supply. What magic is this?
Would throwing more money at the problem ease some bottlenecks in increasing production? maybe? Would it cut months off the time to complete the roll out? Plausibly. However, I don't think it'd make a huge difference to the speed of the roll out over the next six months or so. Some things just take time to ramp up.
They would quite certainly produce no car at all - the economics would not work out. But Teslas, and vaccines, are being produced, so you analogy seems pointless.
At 20/dose, companies could produce N. At 30/dose they could probably find a way to produce more (perhaps by spending money to retrofit an old machine, which at 20/dose wouldn't have been worth it). And at 100/dose they can afford to fly the device manufacturer out to personally oversee sped-up installation.
Deleted Comment
This is a case, where governments should have directly funded the build-up of production capacity. We need production capacities at a level which is economically infeasibly from a vendors perspective. Internationally, we need to produce like 14 billion doses per year. This would mean that whole humanity could be vaccinated within a year. Which is what we need, if we want to erradicate Sars-cov-2. But if we manage to do that, most of those new plants would become redundant and thats exactly why the government needs to pay for them.
> A post-hoc exploratory analysis of immunogenicity in subgroups of participants aged ≥55-<65, ≥65-74 and ≥75 years was performed (Tables S6 and S7). Increases in levels of anti-SARS-CoV-2-spike bAb and nAb at days 29 and post-second vaccination at both the 50 and 100 ug doses were generally comparable across the age subgroups and with those observed in the younger (18-55 years) study participants. Seroconversion rates were also comparable across the age groups and with those in the younger participants. It should be noted that the small size of the ≥75 year-old subgroup (n=22) precludes definitive conclusions to be made.
There doesn't seem to be any link to supplementary material at either the Elsevier page [1] nor the NIH page [2]. The clinical trial registration [3] suggests that there was an update just a few days ago, so perhaps they're just waiting to upload a new PDF?
[1] https://www.sciencedirect.com/science/article/pii/S0264410X2...
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871769/
[3] https://clinicaltrials.gov/ct2/show/study/NCT04405076
> These versions will undergo additional copyediting, typesetting and review, and may not yet have full ScienceDirect functionality. For example, supplementary files may still need to be added, links to references may not resolve yet, etc. The text could still change before final publication.
https://service.elsevier.com/app/answers/detail/a_id/22799/s...
On first read, I thought it was something that neutralizes antibodies, rather than antibodies that neutralize the virus.
My layman's assumption was that the antibodies would always neturalize, so adding the adjectives threw me off the meaning.
Not all antibodies are neutralizing. Antibodies can only bind to a certain part of pathogens, but if an antibody binds to something it might not disrupt what that thing needs to do to infect the body. Relating this to SARS-CoV-2, it looks like if an antibody bind to something other than the spike protein, the virus can still infect cells. As another example, most people have been exposed to at least some other coronaviruses, and of that group, some of those people have developed antibodies that react to SARS-CoV-2. A recent paper [1] looked at if these "cross-reactive" antibodies were helpful in preventing COVID, but it looks like they're non-neutralizing as they couldn't see any effect.
0: https://blogs.sciencemag.org/pipeline/
1: https://blogs.sciencemag.org/pipeline/archives/2021/02/10/do...
The problem with the 50mcg dose is that there is justifiable concern that if you error on the side of low-dosing that the mass vaccination won't work and the public sentiment will turn against it. We'd rather see 95% efficacy with the 100mcg than risk the POSSIBILITY of 60% efficacy with the 50mcg dose. We literally have one shot (or two, pun intended) to get it right the first time. Only 4 months ago, most of the world hadn't even heard of mRNA vaccines or somehow believed it was micro-chipped by Bill Gates. Much of that nonsense has gone away because they're getting unbelievable efficacy that's higher than the traditionally-made vaccines from Astra-Zeneca and JnJ.
Dead Comment
Of course this won't double the number of people vaccinated since Moderna doesn't cover 100%. But every little helps.
Sure, the vaccine efficiency probably drops from 93% to 15%, but it's still better to have a population of 15% resistant people than a population where 1 million get 93% protection and 19 million get 0%.
As more doses come in, the country can similarly divide them and give them as 2nd, 3rd and 4th 'boosters'. They'd probably get up to herd immunity levels with far less total vaccine...
I wonder if perhaps the contracts with vaccine producers stop them doing this? (since it might hurt the vaccines reputation)
Because AFAIK they only started to bill customers for 6 doses per vial when they received official regulatory approval for the 6th dose. Vials delivered earlier were not affected, so any 6th dose gathered from them was effectively free.
> Gottlieb, the former head of the FDA, clarified that the change is not going to be applied retroactively, meaning that all vials previously shipped out are counted as containing five doses.
https://www.cnbc.com/2021/01/25/pfizer-board-member-gottlieb...
I think Pfizer could only start counting the 6th doses after the agencies Ok'd it (and the special syringes were procured)
The real problem I see is that we count vaccine doses as one shot. For Pfizer and Moderna two shots = one dose. It is misleading to show a two vial dose as two doses.
There's already massive incentive to ship first, since there are competing vaccines. If an additional $10B-$100B could result in additional production of mRNA vaccine, it would have been delivered by governments if not by investors.
This is simply a new tech with new techniques. Throwing extra money at a problem when there isn't a chance of increasing production capacity only causes inflation of prices, and rentierism. There is no benefit.
Regulation ensures those in need receive it.
Scarcity ensures demand, supply erodes price.
The ability for companies to charge what they want for the vaccine would ensure only those that could afford it would receive it, and there wouldn't be additional capital investment because that would dilute profits.
Before the COVID-19 mRNA vaccine all mRNA vaccines that had been developed for humans didn't make it past testing. There was no need to have the ability to make them beyond what was needed for research and testing.
And if one of the prior human mRNA vaccines had looked good in the middle of the phase III trial, the low manufacturing capacity would not have mattered. A normal phase III trial takes years, and the diseases the vaccines were for were not pandemics. So even if it takes a couple years to get up to the needed capacity, that would be fast enough.
With COVID-19 mRNA vaccines, we've got (1) an emergency use authorization rather than a normal approval, so a much shorter time between finding out that the thing works and the start of consumer distribution, and (2) it's a pandemic so the number of doses needed is very very high. That's the worst possible combination.