We changed the URL from https://investors.modernatx.com/news-releases/news-release-d..., which is a corporate press release [1], to the most substantive non-paywalled article I could easily google.

[1] https://hn.algolia.com/?dateRange=all&page=0&prefix=true&sor...

Glad to hear it!

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)

Does anyone know how they manage to produce complex microstructures like that, RNA inside a lipid capsule, on such a large scale?

Does these vaccines need an adjuvant to work, or is the change to the affected cells large enough to trigger an immune reaction?

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 ??

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.

https://www.lesswrong.com/posts/Rvzdi8RS9Bda5aLt2/covid-12-1...

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?

Is CureVac still in the race? What other mRNA companies are there that are doing interesting work in the space (beyond COVID)?

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.

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?

(1) https://www.vanityfair.com/news/2020/12/white-house-delays-p...

(2) https://www.wsj.com/articles/modernas-covid-19-vaccine-is-cl...

Hmm super expensive hard to transport Pfizer vaccine ... first to be approved.

Next Moderna ... also super expensive second to be approved.

After six months to a year ... and after making huge profits....

Then the AstraZeneca/Russian vaccine variants will be “found” to be also effective.

We must first wait and let Pfizer make a few billion !!!

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.

[1] https://coronavirus.jhu.edu/data/mortality

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.

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.

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.

>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.

From the linked article[0]:

“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.

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")

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.

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.

Noone has tested single-dose.

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.

I don't think Astrazeneca is banned. maybe they dont have FBA approval.

Also they illegally marketed their psychotic drugs to children under kickbacks from doctors https://abcnews.go.com/Politics/Health/astrazeneca-pay-520-m...

Nothing is "banned".

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 stopped vaccinating people who already had COVID

How would you propose doing this without drawing blood from every single person getting a vaccine?

None of what you said is true...

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%).

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.

> How could we research if the approval was politically motivated?

The analysis of the clinical trial was published in a very reputable and peer reviewed scientific journal [1,2].

> How can I know if this is actually safe?

In the reports [1,2].

If you believe that data is fake then I am afraid you just not want to be convinced.

[1] https://www.nature.com/articles/s41586-020-2622-0 [2] https://pubmed.ncbi.nlm.nih.gov/32991794/

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.

It's $40, not super expensive.

600 million doses would cost $25 billion, a trifle compared to how much the pandemic is costing.

  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

What exactly is wrong with allowing a company to profit from performing a literal miracle?