One key advantage of the Moderna one versus the similar Pfizer/BioNTech vaccine is that it doesn't require deep freeze storage, only regular freezing temperatures. (-90º C for Pfizer/BioNTech vs -20º C for Moderna)
> Moderna spokesperson Colleen Hussey explained to NPR in an email that its vaccine doesn't need to be kept so cold because of its particular "lipid nanoparticle properties and structure," and because the company has learned from experience — it's developed ten mRNA vaccine candidates already. "Now we don't need [ultra-cold conditions] as the quality of product has improved and [it] doesn't need to be highly frozen to avoid mRNA degradation," Hussey explained.
and
> It's possible that Pfizer's vaccine could eventually be shown to be stable in somewhat warmer conditions — or for longer times out of the freezer.
They're saying that the differences are secret, and they're not gonna release the specific structure of the LNPs and why the differences are there. The equivalent of having two proprietary binaries that both accomplish the same task, but have different code, and the reasons why are secret as well.
And we're accepting this on the first mRNA vaccine ever to be used on a massive scale, all to protect their profits before the rest of the world can start producing vaccines. Yes they spent a lot of money and time creating the vaccine. Now open source it and let the rest of the world save their citizens.
> Yes they spent a lot of money and time creating the vaccine. Now open source it and let the rest of the world save their citizens.
And who’s going to pay for it? The whole PPE shortage was exactly because of this entitled attitude. If you artificially limit prices, you’ll only limit the supply (to possibly nothing, as vaccines have high upfront costs), and enable scalpers.
One obvious solution is to have a UN initiative that buys the IP and opensources it. I don’t know how hard this is. Generally, one big problem is the lack of gratitude on the part of freeriders. Otherwise, the goodwill it generated for the sponsors would probably be enough to make it happen.
PS: I live in Iran. I am not defending my privilege here.
Ideally, they would realize that moral responsibility to save lives is greater than money in this case. I don't think money would even be a problem, public pressure would be enough if everyone knew what was at stake. The companies capable of manufacturing would still make money by selling the vaccine to governments and people.
Probably every doctor and nurse feels moral responsibility to save lives is greater than money in any specific case. But if you cut all their compensation to minimum wage plus a bit, I doubt many will keep working in health care for very long.
It doesn't matter now because that's not some ingredient you can bolt on. It was part of the initial design process.
Sure, they could have shared all their secrets, and BioNTech theirs. Then, they would have come up with the same vaccine candidate and run two identical trials. Which would've been quite useless and far more risky.
Those LNPs have historically caused adverse reactions, per their 2018 SEC filing, hopefully their upgraded versions are improved and do not cause those reactions; I am hopeful.that they have, because of the reported results of their current clinical trials, but it is a data point:
"Most of our investigational medicines are formulated and administered in an LNP which may lead to systemic side effects related to the components of the LNP which may not have ever been tested in humans. While we have continued to optimize our LNPs, there can be no assurance that our LNPs will not have undesired effects. Our LNPs could contribute, in whole or in part, to one or more of the following: immune reactions, infusion reactions, complement reactions, opsonation reactions, antibody reactions including IgA, IgM, IgE or IgG or some combination thereof, or reactions to the PEG from some lipids or PEG otherwise associated with the LNP. Certain aspects of our investigational medicines may induce immune reactions from either the mRNA or the lipid as well as adverse reactions within liver pathways or degradation of the mRNA or the LNP, any of which could lead to significant adverse events in one or more of our clinical trials. Many of these types of side effects have been seen for legacy LNPs. There may be resulting uncertainty as to the underlying cause of any such adverse event, which would make it difficult to accurately predict side effects in future clinical trials and would result in significant delays in our programs"
I read that Pfizer/Biontech is currently testing whether they can go with higher temperatures, but those tests aren't finished yet, because the first priority was to get the patient data, and there they did what they expected will be safest and most likely to work.
It may very well be that later on they'll change the freezing requirement later.
Different lipid nano particles, or maybe just stability testing. The vaccines could be stable at lower temperatures but the companies haven’t had time to prove it by letting the vaccine sit in a fridge for months.
The answer is "there is probably no difference, but Moderna has more experience with mRNA vaccines and felt good about the -20 requirement, but Pfizer is new to mRNA, and didn't":
As someone who has been involved in stability testing before, I doubt this is really the case.
In order to justify your stability, you need data to submit to the FDA (they don't take your word for it). When doing your initial stability studies, you try and collect data for the most ideal conditions - no refrigeration needed, stable for X years from room temperature to 30C (to account for conditions during shipment).
No doubt Pfizer lined up a number of early stability studies testing -80C, -50C, -20C, 0C, etc. They recognize that needing a -70C cold chain is a logistics hurdle. If they could avoid it at all, they would have pushed for it and had data to back it up.
Though in practice it’s more complicated. Basically, make predictions based on accelerated testing and then validate them in real time tests. So, if things hold up at 3 and 6 months real time you can probably trust them over longer timeframes.
Exactly. Plus dating tends to get extended post-approval.
If Pfizer has a short-list of candidates back in May, they could have had 6 months of stability data at approval.
They can keep those studies going and by next May have 12 months of data for the FDA to review and potentially update the transportation and storage requirements.
Yea, prescription drug manufacturers have little incentives to seek multi year shelf lives. Combined with the slow approval process real time testing is likely considered sufficient.
I think you summarized it well. There is little incentive to test the limits of stability as manufacturers typically control channel inventory quite tightly. I know my company targeted maybe 14 days on hand? So going much beyond 2 years stability didn’t make much sense as most product was consumed well before it expired.
Not OP, but this is the same way lightbulb or hard drive manufacturers can claim "greater than 50,000 hours of operation". Instead of testing for over a decade, they test many samples over a shorter time duration, and then they extrapolate. Like any other extrapolation, these estimates have their caveats. But for biological reagents, something like an exponential decay is often considered reasonable.
Accelerated studies. Usually you test stability for shorter periods of time under harsher conditions. It’s not perfect, but if your product is fine at 50C for 2 months, it’ll probably be fine refrigerated for 12 months.
Assume that the reaction rate (shelf life) versus temperature relationship is described by the Arrhenius equation or some other model; perform experiments at elevated temperatures, and extrapolate to lower temperatures.
> but Moderna has more experience with mRNA vaccines
Let's keep things in perspective, please. This EUA is for Moderna's first product with any approval whatsover from the FDA. The lipid coating is a way for encasing the mrna vaccine in a kind of plastic for entering the cell.
Isn't the Pfizer/BioNTech one marked at this temp because they simply didn't have enough time to really figure out the safe temps?
I recall reading an article that mentioned -90C as the "safe shot", meaning they can be 100% certain that the vaccine is stable at this temp but it might be stable at much lower temps.
Pfizer is spending a considerable amount of money on their cold chain, for example buying up pretty much all ultra-low temperature freezers they can find. I personally doubt they'd still be spending that money if they needed it, there's been plenty of time for a stability analysis by now.
> I personally doubt they'd still be spending that money if they needed it, there's been plenty of time for a stability analysis by now.
I don't believe your logic follows. There's a lot riding on this vaccine working as advertised, thus there is considerable pressure on Pfizer/BioNTech to deliver on that promise. If they know their vaccine is at peak effectiveness when transported at -90ºC and that the effectiveness drops if handled at lower temperatures, and if time is critical as it is, then they have all the reasons in the world to just play it safe by going with the costly but reliable option.
That's true, on the other hand, consider that Moderna has lowered storage requirements twice in the past four months. This gives us three options, Is it Moderna taking more risks, Pfizer being more risk-averse or is the Moderna one inherently more stable?
> That's true, on the other hand, consider that Moderna has lowered storage requirements twice in the past four months.
Moderna's vaccine was the second to enter the US market. If Pfizer/BioNTech delayed their vaccine to work on lowering the temperature requirements, Moderna would eat their lunch, and Pfizer/BioNTech would be relegated to second place on the place it matters the most: the history books.
As is, I'm sure that Pfizer/BioNTech are already working on improving temperature requirements, while leading the race.
> This gives us three options, Is it Moderna taking more risks, Pfizer being more risk-averse or is the Moderna one inherently more stable?
I have zero insight on the situation, thus I can't really tell. However, it's clear that each and every single actor in the story, from biotech companies to politicians and also regulatory bodies, is taking way more risks on this issue than what they would otherwise take.
If anyone is curious how this difference will make an impact in the big picture, I cannot recommend highly enough the Youtube video on Covid vaccine logistics by Wendover Productions (I can't search youtube at work to provide a direct link but it should be easily searchable).
Yep, my understanding is that the mRNA eventually degrade and disappear from your system, but your system requires more time to build enough antibodies.
The actual study results show the vaccine is highly effective within 10 days of the first dose.
Honestly a bit shocked based on the results and the number of lives that could be saved by effectively doubling the number of available doses that they didn’t try to get it modified to a single dose regimen.
Seems to me like just another way the FDA has screwed up this whole rollout.
Two doses is very common for vaccines because this is based upon how the immune system responds to real infections. The first dose will initiate a primary immune response. The second dose will act as a "challenge" to trigger a secondary immune response.
It sounds like one dose is enough to make you much less likely to develop serious symptoms or symptoms at all, and two doses gives you close to immunity.
Absolutely, after the first shot you do have immunity but it's not as fully developed compared with having two, so it will take longer to respond than with two, and that does present a larger window of opportunity for the virus to cause problems.
This article [1] has a section with several references on that, with the most used technique [2] being depicted in fig. 3 (this is from 2016 so there might be a more recent technique around now).
The basic principle is to mix a solution with lipids and one with the mRNA and pump it through a channel with herringbone-shaped incisions that generate turbulence in the fluid. Apparently, the turbulence makes lipids surround the mRNA and stick together to form the nano-particle.
So to quickly summarize they use fluid dynamics and force and whatever sticks through this process will be useful.
I wonder what the rate of lipid-surrounded mRNA is after the process. Say you fire 100 mRNAs through this construct, will 90 of them be surrounded by lipids afterwards? Or 30? Or 100?
i'm surprised absolutely noone here talks about the fact that we have absolutely no idea what the long term consequences of this new tech are.
We've all seen people advocating new wonderful technological solutions that fail because of unknown unknowns, in every field. That's just the rules of the R&D game.
In that case we're seriously thinking about injecting a new kind of drug to the whole world population based on a couple of short term trials, for a desease that is only lethal for far less than 1 percent of the population ( and in general, only the most fragile 1 percent).
I'm just like everyone and i find this new arn cell transcription machinery hacking absolutely insanely great. And i also think it looks safe from what the expert are explaining.
But is it safe enough to have it taken by everyone in the world ??
The case fatality rate is around 1.8% in the USA [1]. Current population is 330 million. So if the entire population becomes infected that’s 5.9 million dead.
The case fatality rate would likely increase as we overwhelm healthcare resources, so it could be even worse.
1% may sound trivial but it becomes meaningful at the scale of a population. The benefits of the vaccine far outweigh the risks.
I was injected yesterday along with my fellow emergency department and ICU staff. People seemed giddy with hope and relieved to become protected. If you see enough people die of covid then the risk of the vaccine seems trivial.
Thank you for being willing to take the still-nonzero risk of a lightly tested vaccine.
I am fortunate enough to be a remote employee with little need (or desire) to interact in ways that I could spread or receive Covid-19, so I personally will wait a while for more data on safety and efficacy.
> The case fatality rate is around 1.8% in the USA [1]. Current population is 330 million. So if the entire population becomes infected that’s 5.9 million dead.
It won't get anywhere near that, as it doesn't take into account asymptomatic (I've seen estimates in some areas as high as 20:1, which would put the number dead at ~300k) and due to herd immunity not everyone is going to get infected anyway.
That 1% have the ability to devastate the healthcare infrastructure.
ICU beds are dollar for dollar the most expensive resource in healthcare today.
Not to mention the rarity of qualified healthcare workers who are trained in working in the ICUs and the risk of losing them for 2+ weeks if they get infected.
> That 1% have the ability to devastate the healthcare infrastructure.
Additionally, other people will die at a higher percentage from other-than-covid reasons because covid patients are taking up all the resources, which can no longer be used to treat other patients.
Okay, we've researched mRNA medicine since the 90s. But have similar medicines been given to a million people? Have those been tracked for three decades? We're talking about scaling that up by a factor at 10-100+, and giving it to millions of healthy people with many decades of life ahead. What if some serious adverse reaction happens ten years later, to 0.1% of the 20-year olds who take it today? Worth it?
The efficacy of the new mRNA vaccines is fantastic. It's a no-brainer to give them to people with a high likelihood of having a serious covid case.
Maybe it's justified to also give it to everyone else, to mitigate the economic effects of the epidemic. But asking this question is qualitatively different than what you hear from people who are normally skeptical towards vaccines. This is a completely new type of prophylactic, there is potential of an unknown unknown.
I'm typing this contrarian comment mostly to document that I've thought about it, in case, heaven forbid, we make a horrible discovery about it in 2025.
Honestly - aren't there researchers working in the field thinking similar thoughts? Is it such a taboo interjection that they don't dare speak it out loud out of fear of being compared to antivaxxers? I don't believe that it's an excessively cautious concern.
It won't be taken by everyone in the world. There are countless vaccines being developed. The two mRNA based ones were the quickest to fulfil the criteria of their phase three trials. The AstraZeneca/Oxford vaccine and Sputnik V are based on more conventional methods (adenovirus vector) for example.
Also: the implication of your statement about the "most fragile 1 percent" is that their lives are worth less than others. I cannot begin to describe the disgust I am feeling towards such an inhumane attitude.
"inhumane attitude" could also be a good qualifier for using the population as lab rats.
it's called a tradeof , and public policies is doing it all the time, including accepting people dying for the greater good of others. Otherwise we would have banned cars a long time ago.
So vaccine looks more dangerous to you than COVID, despite numbers showing that's not the case? 20 in 1000 dying from COVID-19 is somehow acceptable, but two in hundreds of thousands getting some allergic reaction is not?
How does one even justify that logic?
Wait until countries decide to close their borders to people that haven't been vaccinated.
Most countries in asia already ask for a negative PCR test for tourists, and some (like malaysia) have been in lockdown for almost the whole year despite having had less than a thousand casualties in total.
I wouldn't be surprised if madness reaches another level very soon.
Ok, what the mechanism for the long term consequences would be? mRNA itself is gone in days. All what's left is antibodies and some immune memory which should be the same as if you had real COVID. Is that more dangerous than catching covid which may affect your body in many more ways than vaccine which makes your cells to produce a particular protein?
I do not know what the long term effects of the glass of water I just drunk will be.
The thing about "unknown unknowns" is that they are unknown. It's like asking "what could possibly be outside the edge of the map, surely it's more of the same".
This isn't a matter of water flowing downhill through a pipe or a piston moving through a cylinder. Although we have a good understanding of the process, we don't have decades of extensive engineering experience to give us empiric reassurance that there are no gotchas. We didn't put a billion people into airplanes nine months after the first commercial airliner was developed.
Sure, hopefully our current understanding is good enough and there are no long-term side effects. But it's naïve to assume a likelihood of 100%.
Although the elderly and sick have a high likelihood of a serious covid case, young and healthy people are exceedingly likely to have a mild disease. These probabilities are what you have to judge the confidence of long-term vaccine safety against.
This is not necessarily specific to the mRNA vaccines, but one potential consequence of population-wide deployment of a 90% effective vaccine might be to create selective pressure for a more virulent strain of Covid without actually eliminating it.
By that logic, we'd be ravaged by polio, the plague, tetanus, super-smart bears, and evil spirits.
We should also stop all research.
(I was going to also sarcastically suggest disbanding the military. But that actually happens to sort-of work along the lines you have in mind, because we can disarm tit-for-tat along with everyone else. So what we really need is for COVID to evolve faster, until it is capable of negotiating a truce and make strategic decisions)
The polio vaccine, as administered, is over 99% effective, which is an order of magnitude difference.
If what I wrote is correct I don't see how it lends itself to "stop all research" as opposed to "wait until we have a more effective vaccine." I'm not even saying it's a greater than 50% probability, but it is a risk.
>is it safe enough to have it taken by everyone in the world ??
Alternative: if we don't know it's safe, better have everyone take it, or at least as many as possible. That way there's no reliable control group to compare outcomes, and no one can blame the vaccine, and it's easier to blame other external factors or say we don't know.
This is (systemically) the general approach taken with many environmental toxins. It's only when unfortunate, acute "cancer clusters" etc appear that some really nasty chemicals which are prevalent everywhere - like PFAS, etc - come to attention.
Anyone knows why they insist on both doses given the limited supply of the vaccine and the marginal increase in effectiveness with the second dose? I would imagine every single day counts.
“Yes, Moderna’s vaccine prevents transmission. One dose is good for reducing infection by 63%, two by over 90%.”
The number of people you need to vaccinate with a 63% effective vaccine versus a 90% effective vaccine is a huge gap.
There are two issues with vaccines that staring at these numbers won’t tell you:
1. Not everyone is going to get vaccinated.
2. The number of people who will get vaccinated is directly correlated with public trust.
If you release a vaccine that is 63% effective, the “this vaccine doesn’t work crowd” and their hugely amplified voices on YouTube and social media will be exponentially worse.
That snowballs into fewer people being vaccinated. Unlikely for us, with a less effective vaccine we need far more people being vaccinated.
So you want a more effective vaccine because fewer people need to get vaccinated, more people will trust the vaccine, and more people will get vaccinated.
(To pre-empt the bad-faith replies, this does _not_ mean we would sacrifice another six months to get a 98% effective vaccine (if it were possible) versus starting now. It’s a balance, of course.)
Also very important is that a second dose isn’t just for effectiveness, it’s to boost the immune system’s response so that the conferred immunity lasts significantly longer.
[0]: I struggled through this article. I find this self-congratulating “I’m smarter than everyone and I told you so in this other blog post” writing insufferable.
I'm not American so I could be way off on this, but I can't help but wonder if the politicization might've actually helped in this case? My big assumption is that Trump supporters would normally be more skeptical of vaccines. If non-supporters would trust the vaccine regardless, then perhaps politicizing it just means that more Trump supporters would also take it?
This will be overcome. It was about trusting the scientists instead of the White House. I'm fine with it now. But didn't they pressure that CDC director to approve it that day or get fired? They were probably going to approve already. But what if they weren't far enough along and some of this nonsense would've played out like that? It'd have been very harmful for the trust in the vaccine.
I trust the scientists and doctors who've said it's safe and explained the reasons it was approved faster than normal that have nothing to do with Trump, aside from his botched preparing for and handling of the pandemic necessitating it.
As someone that has been preparing for an influenza pandemic since 2005 I can tell you that the yearly tri or tetra valent influenza vaccines each year are often, in the last decade mostly, down near 50% protective. And you don't get 2 influenza shots.
This is not something new or special. And people being ignorant should not change how things are properly done. Yes, they're going to freak, but it's because they're idiots. Don't base behavior on what they think. Accomidating them will not change their behavior at all. Their behavior does not reflect external realities.
This argues against only giving one dose instead of two. But no one is proposing that.
The argument is that while there is a vaccine shortage, it is better to give as many as possible one dose, instead of giving only half that many people two doses, leaving the rest unprotected.
When available, everyone gets the second shot, which should work just as well 6 months later.
Do you have clinical evidence for that? I doubt it. OP still has a more valid point. Public trust in the vaccine and its apparent effectiveness ASAP after the vaccination campaign begins will be gigantic factors in its success.
We all know that a hard lockdown brings down the new-infection numbers WEEKS after beginning the lockdown, yet there are still a lot of people on Twitter, YT and at demonstrations (at least here in Germany) where folks are angry that the lockdown doesn't work 2 DAYS after its beginning.
The amount of truly wary/ignorant people out there is around 5-15% of the entire population in Germany and handing out a 63%-effective vaccine will be fuel to their bullshit stories.
I wish people would start taking this more seriously. We have a huge chunk of the population (5-15%) where discussions don't work anymore because their arguments aren't based in a common reality (e.g. "viruses exist and may pose a threat" is surprisingly often not a supported opinion).
> We all know that a hard lockdown brings down the new-infection numbers WEEKS after beginning the lockdown, yet there are still a lot of people on Twitter, YT and at demonstrations (at least here in Germany) where folks are angry that the lockdown doesn't work 2 DAYS after its beginning.
In the spirit of understanding, in your words what are the biggest arguments against forcing a hard lock down?
I'm no epidemiologist, but I understand this is the how booster vaccine shots typically work.
I care less about public trust and the PR angle, and more about getting as many people protected as possible. If dumb people say dumb things matter much less.
The lesswrong quote seems to be misleading. It links to an article that says the vaccine may prevent / reduce transmission but that it hasn't been proven yet. Did I miss something?
The British Medical Journal has an article that makes the point, including quotes from Tal Zaks of Moderna, that the studies aren't designed to be statistically significant indicators of disrupting transmission, preventing hospitalisation, or even preventing death:
So, from what I can tell. It isn't proven to disrupt transmission or reduce hospitalisation/death. It would require much larger or longer studies, which they have opted not to do.
I think lesswrong is wrong here. I looked at the document that lesswrong links, and I couldn't find any statement about effectiveness of the vaccine in preventing infection after two doses.
It's not an unreasonable suggestion (and a lot of people are making it now), but the risk with a single dose is low persistence. We know that the first dose has high effectiveness in the first month, but it may trail off sharply. Or it might not. Since we haven't tried a single dose, we don't know.
In animal studies, the second dose was required for a durable response, that's why Pfizer decided to go with it in their trial.
They played it save when designing the protocol. Better to err on that side, than to risk failure because you chose a dose that's too low.
Given that's what they trialled, there really isn't a mechanism that would allow either them or the FDA to change the protocol from what was tested.
Yes, this is annoying. You can make that educated guess and not show up for your second shot and you'll probably help someone.
But medicine has a long history of people being rather convinced of theories that made an awful lot of sense and killed an awful lot of people.
At some point, they noticed. The double-blind trial became not just the preferred method or something like that. It became absolute gospel. Anything else is considered the GOTO of injecting people with... stuff: Even if it's exactly what you believe is needed right now, it's just not going to happen.
See also: "masks don't work" ( = "even though it sounds like a good idea, there is just as much actual evidence for their usefulness in preventing viral diseases right now, January 2020, as there is for crystal healing. Give us a month and we'll have data")
"But medicine has a long history of people being rather convinced of theories that made an awful lot of sense and killed an awful lot of people."
That works for both sides, both the true believers and the skeptics. Both sides are absolutely convinced that they are right and the other side's belief will kill people. At least one side is wrong. Both have their reasons, both appeal to history, both appeal to science. It is a confusing time to live.
My impression is that the consensus is reasonably strong that masks work in and of themselves, that is - they do act as a physical barrier against transmission, but, most infections are happening at e.g. family gatherings and in households, so the actual effects of masks writ large are more muted than proponents argue. Basically, it's like saying seat-belts work, which is obviously very true, but regarding them in a kind of isolation that forgets about setting speed limits.
If every single day counted, they would have done challenge trials. What counts is following the FDA's process, and the FDA's process says that you have to administer it in the same way as the trial. No one at the FDA is going to go out on a limb just to save a few thousand lives.
Challenge trials don’t work when 40% of infected are asymptomatic. And challenge trials especially don’t work when 15% of cases require hospitalization and ICU beds are already maxed out.
I don't see how the asymptomatic fraction makes a normal trial superior to a challenge trial.
As for the hospitalization and ICU, those numbers are inflated, but regardless, in order to pass the trial, the same number of people need to be infected in the trial. The only difference is that while you're waiting for a few dozen people to be infected naturally because you gave them a placebo, millions are being infected and thousands are dying daily.
> Later, a vaccine candidate that has been proven safe in clinical trials could be given to a group of healthy adults in this age range, who are then exposed to the virus in a controlled environment. They would then be closely monitored by medics and researchers to see if the vaccine is successful in preventing infection, as well as identifying any side effects.
When the asymptomatic rate is high, it’s hard to determine if the vaccine is truly works, and to what degree. If 40% of people are asymptomatic then that would theoretically mean that 40% of challenge trial participants won’t show symptoms. Does that mean the vaccine is working? Who knows. It could be working, it may also not work.
The only way to do it and get real results is to use a challenge trial only on the elderly population where the asymptomatic rate is low and where the symptoms are exaggerated. This would mean though that if the vaccine didn’t work you would overwhelm the hospital system with a lot of sick elderly people who require the most care, when the healthcare system is already overwhelmed.
Being ethical and being “ethical” according to professional expert ethicists is also not the same thing. If I learned anything this year, it’s that opinion of professional experts at ethics should not be considered when deciding who gets last piece of cake, much less in life and death scenarios.
Citation needed for that 15% number. Even if it’s true, it absolutely isn’t true for all age groups. Give to 20-29 year volunteers. There were hundreds of thousands who volunteered.
What our (Lithuania) officials say is that about 5% of the cases are hospitalized.
We are close to the top by the number of new infections per 100000 pop.
I'm not an expert, but my understanding is that the error bars on efficacy for the single dose are quite large, just because of how the studies are conducted. Moderna's lower bound was below 70% with a single dose, and Pfizer's is below 30%. That's not to say that a single does is definitely not effective, just that there's a lot more uncertainty, and so the bounds are much looser. We also don't know whether giving a second dose a few months later rather than a few weeks later would work as well.
Depending on supply forecasts, it might be worth running a new trial to get a better handle on the efficacy of a single dose, but going that route now would definitely be a gamble. Especially since we're formulating this single dose hypothesis after having run the experiment and seen the results, which is always a dangerous approach.
Still, the data do seem to suggest that it's very plausible that a single dose would be sufficient. If things get bad enough, or supply is low enough, maybe that's a gamble worth taking.
One thing to consider is that vaccine production is going to scale up in time; since the second dose is a month after the first, giving two doses instead of one will not mean that half the number of people will be vaccinated.
Assuming, for the sake of the argument, that vaccine production doubles every month, at any given point after the first month the amount of people that have received at least one does will be a bout 2/3rds of the single dose protocol.
In this case it may sound like too much nitpicking, but the general principle is that you don't roll out something you haven't tested in a trial. In general this is a good principle. I hope they'll do trials comparing single to double-dose soon.
Are mRNA vaccines safer than traditional ones? In the long run, which one will have less side effects? As far as I know, Both US and Europe are only going with mRNA vaccines for COVID. Is it intentional or just because there is no traditional vaccine that completed Phase III trials?
Professor Shane Crotty, PhD answers a series of COVID 19 vaccine questions including what are the chances of long-term side effects? How safe is RNA vaccine (i.e. Pfizer / BioNTech an Moderna Vaccines) technology? How long does mRNA from a vaccine stay in our cells? What else goes in vaccines? How long does immunity last? Why are T-Cells so important? Why does Pfizer's vaccine need to stay SO cold?
I looked the video and he says that based on vaccine literature, for the past any important vaccine safety signature was clear within two months meaning two months is enough to conclude whether a vaccine is safe or not. However, I think his answer seems a little bit superficial. Isn't the most part of the vaccine literature based on traditional vaccines? Yes I know that mRNA is not that much new but is literature on long term side effects of mRNA vaccines extensive?
Seems like people prefer to downvote rather than try to give a compelling answer to the question "is the literature on long term side effects of mRNA vaccines extensive".
If the argument towards this question is overwhelming, surely someone has made a lecture on it somewhere.
> Seems like people prefer to downvote rather than try to give a compelling answer to the question "is the literature on long term side effects of mRNA vaccines extensive".
I think it might be because people are confusing asking questions with being against something. I am neither against vaccines nor mRNA vaccines particularly. I just genuinely want to learn the details. I think it is important to know upsides and downsides of each vaccine out there since there are several alternatives.
I have noticed this sleight of hand being used in a few different mRNA explainers. The two month window which has usually been sufficient to establish the safety of traditional vaccines isn't really applicable here, unless we have some reason to believe this new type of vaccine will present side effects and complications in the same way over the long term. But we don't have a good reason to believe anything about them in the long term because it has never been studied.
The mechanism of action is actually a good reason to believe lots of things about them long term.
The mRNA is delivered, causes cells to express proteins and is naturally broken down (it's normal for the body to sweep up mRNAs over time).
Once the mRNA is gone, the long term effect is the immunity, which there's no reason to expect it to be different than immunity to similar antigens, which is something that is well studied.
So the immunity side of it is not a radical departure (antigens are presented to the body) and the delivery/mechanism is quite clear and has a natural brake (mRNA degradation).
The latter. Many countries have bought a mix of both, the advantage of mRNA tech was always its adaptability hence why these are coming out first. Oxford vaccine is reported likely to be approved for use in UK in less than two weeks’ time, for roll out first week of Jan
If they stopped banning Astrazeneca too, and stopped vaccinating people who already had COVID, we could be done within 60 days. Astrazeneca is well above the FDAs original safety and efficacy guidance and something I'd be glad to take and give my family.
AZ accidentally ran their first trial with only half the intended dose. For some reason, this turned out to work better than the intended regimen (90 % vs 60 % in the other trial).
When they noticed the mistake, they pretended it had been their intention all along.
That's one troubling error, one surprising result that doesn't fit expectations and could, therefore, indicate other, potentially dangerous, problems in thinking or execution, and one deliberate lie.
Personally, I'd tend to agree with you and would probably take their vaccine if offered.
But that's something entirely different than allowing it to be given to millions of people. Getting this wrong would lead to a total breakdown of trust in institutions, and, in due course, a few democracies as well.
To insinuate some conspiracy given these circumstances is evidence for the mechanism of that breakdown, as well as irresponsible and, frankly, amateur populism.
And it turns out the cohort who received the half dose was on average younger than the total study population, this explaining the apparent improvement in efficacy
As far as I can tell, the virus is more prevalent among younger people. Since infection, not death, was the primary endpoint, and also because medicine hasn't used that sort of wishful reasoning for about a hundred years, the age difference doesn't explain anything.
it certainly does, younger people have stronger immune systems, and therefore generally react better to vaccines than older people. The stronger the immune system reacts to a vaccine the better, since that usually ensures that there will be an immune-response to the actual virus as well.
It is utterly impossible for two trials of that size (thousands) to result in 60% and 90% effectiveness, respectively, by chance. I can't quite do a t-test in my head any more, but I'd guess that difference passes the 5% significance threshold somewhere around n=30.
Hard to imagine that infection and recovery from the actual virus confers less immunity than the vaccine, but even without knowing that, it seems reasonable that people who have already recovered should be a lower priority for vaccination than more at-risk groups.
It’s not hard to imagine, it’s a well observed phenomenon in other diseases like HPV. Antibody titers were higher for the mRNA covid vaccines than convalescent plasma if I remember right.
Most people probably are at lower risk, but some people are dying from reinfection. They certainly weren’t.
The AstraZeneca vaccine doesn't have enough supplies for that when you count all the countries that have ordered it, and isn't effective enough to create herd immunity by itself (most likely 60-70%).
I am concerned that the Pfizer vaccine was put on hold [1].
I am also concerned that Moderna has never produced ANY drug beyond the third stage before. [2]
How could we research if the approval was politically motivated? How can I know if this is actually safe?
It was not "put on hold", rather as many experts expected, especially with the state of the current administration, mass distribution and coordination is a clusterfuck. Which, to be fair, is a very challenging problem with a lot of minutia and moving parts. But "your amazon product will take another day to ship" is very different from "your amazon product is broken".
If you're worried that it was rushed by US politics: the "Pfizer" vaccine was made by Biontech, a German company, and has also been accepted (earlier, even) by regulators in Canada and the UK.
Shipping and distribution problems have nothing to do with safety. There's a lot of data on what side effects the trial participants got, how the vaccine compared to placebo, etc. which has been published by the FDA. With tens of thousands of trial participants, we can be pretty confident that serious side effects are rare.
> I am also concerned that Moderna has never produced ANY drug beyond the third stage before.
Have there been a lot of disease outbreaks preventable with an mRNA vaccine before? To make a product, you need customers. Whatever research we did to deal with SARS and MERS became moot when people stopped spreading the diseases; maybe Moderna could have delivered a vaccine, but there would have been no customers because other containment measures limited the spread.
My outsider impression of Moderna is that they had all the technology ready to deal with something like COVID-19, but there was no COVID-19 until now.
The fact that Pfizer/BioNTech independently produced a similar product on a similar timeframe is a pretty good indication that the technology was ready, and was just waiting for a market.
Ah yes, it's definitely a conspiracy, not the fact that the Biontech/Pfizer and Moderna vaccines are RNA based, which are far faster to make, but which also are known to break down at high temperatures while AstraZeneca is a traditional vaccine.
Yep, it's definitely not the logical reason but Big Pharma and the US government and Germany at it again.
I wouldn't say far faster. Russia and China have both come up with vaccines in a similar amount of time. We haven't seen any details on how effective they are compared. J&J is making a more traditional vaccine and it should be finishing up the Stage 3 study in a month or two and be ready for approval. They're hoping it will be a single dose vaccine
> Belgium’s budget state secretary, Eva De Bleeker, posted the price list on Twitter, with the amounts of each vaccine that her country intends to buy from the EU. The tweet was quickly deleted, but not soon enough to prevent interested parties taking screenshots, which have now made it public knowledge.
This is the list of what the EU is paying:
Oxford/AstraZeneca: €1.78 (£1.61)
Johnson & Johnson: $8.50 (£6.30)
Sanofi/GSK: €7.56
Pfizer/BioNTech: €12
CureVac: €10
Moderna: $18
Well hundreds of millions have already flowed into every major pharma company for development costs, so the price for tax payers in every contributing country is substantially higher than $40/person. That's just the price an individual may see.
You're kidding right? The whole operation "Warp Speed" was a bit over $10 billion, that is a pittance compared to the trillions spent to keep the economy from collapsing.
That is true, and likely one of the reasons for that favorable EU deal.
But what's also correct is: neither Pfizer nor BioNTech did accept money from the Trump government (except as payment for the finished product once it was approved of course), which is what the OP probably meant. There's a huge difference regarding the potential for politicization between this particular government and any other sane government on this planet, and especially the German one that's currently being led by a trained physicist.
No, that's (roughly) the per dose price the US is paying for the vaccine (there's no individual fee here for the vaccine, I guess there can be an administrative fee, but that won't go to the manufacturer, it will go to the health provider doing the vaccination).
This is why I was so angry to find out that the Trump administration passed on 100 million doses. Are you kidding me? And they didn't have to pay for them if it wasn't proven to be effective. There was literally no downside! This has just been a terrible Presidency from all angles.
If Trump had stockpiled even more doses he would just be called a mass murderer for hoarding the initial supply. America has enough of the first round of production locked up.
Their purchase targets across all the vaccine candidates should have been in the billions, with the idea of distributing any excess (FDA approved) vaccines around the world.
The US has 100 million doses of Pfizer and 50 million of Moderna, enough to cover a bit under half the country. Then, it has 500 million of the Oxford vaccine. Altogether, this is more than enough to cover the country. And then it has the option to purchase more..
No, I read that the doses reported by the government are the full two doses, so if there are 100 million doses, then the government has 200 million shots.
I think Gov should buy the vaccine and provide it for free. Private companies should rightfully charge a premium to the governments as they took: 1) Enormous risk 2) Expediency 3) Investment of talent 4) Demand is through the roof; all this even if the governments were involved in hedging the risk for spinning up manufacturing lines.
In the US that is what is happening - no one is paying for the vaccine.
It is intellectually vapid to get worked about the fact companies are making a $15 marginal unit profit on a vaccine that has 10x the utility of the average annual physical but costs 1/10th as much.
[1] https://hn.algolia.com/?dateRange=all&page=0&prefix=true&sor...