> Now, the thing is that you can’t just sequence a virus, do bioinformatics, synthesize mRNA and package it into a nano particle.

You can, and that's exactly what was done. However, out of the 10 or so candidates, they selected a few of the more promising ones to continue research.

They are fast to develop. However, there are other steps in the pipeline that aren't so fast.

> The mRNA that gets packaged needs to be modified (I believe with alternative bases) to achieve desired effect.

That's the easy part. The full mRNA sequence is not that large (https://berthub.eu/articles/posts/reverse-engineering-source...) and many of such substitutions can be done by algorithms. Now, maybe the modified protein won't fold right. That's not as easy (although, we can compute how it will fold now).

> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants.

If we were reckless and just wanted to inject someone with the latest update, this could be done in a matter of days. Human trials took months and people still complained that it was 'developed too quickly'. Then there's logistics.

And yes, AlphaFold is a major milestone, but I don’t think we’ve solved protein folding for good.

I'm sure there is also the commercial concerns about cannibalising their own product. Would you take the 1-strain BioNTech vaccine if you knew that a 5-strain is also in circulation?

*when paid annually

First, BioNTech (not Pfizer) had 10-15 years to research, develop and test vaccines against new zoogenic Corona viruses. There was literature regarding the modification of the spike protein even before SARS-CoV-2 hit. BioNTech had either SARS or MERS candidates years before the pandemic.

Second, we cannot compute "how it will fold" either.

Third, discussions on HN always, always leave out the hard and messy parts: Wet lab and patient studies.

I am a huge fan of mRNA vaccinations, but the understanding of their potential is hugely different between the "hacker world" (HN, Twitter computer scientist bubble, etc.) and the biology world.

It doesn't seem meaningful to define development time without including all the steps required to provided an available vaccine to the public

That's why the codename for the AstraZeneca vaccine is ChAdOx1, it's a Chimp Adenovirus as host for the sequence. Take this mild uninteresting chimpanzee virus, but tweak it to tell human cells to produce your arbitrary sequence instead of itself. The humans become immune to whatever your sequence was (and maybe to Chimp Adenoviruses?).

I'm sure there are reasons this might be better in some cases, and it involved less bleeding edge technology which made it a safer bet in a pandemic, but the mRNA approach seems obviously more general and even perhaps more re-usable.

Which is a major problem with this technique. One of the other vaccines (J&J?) used a relatively harmless human virus and as I recall, some people with previous exposure had no effect from the vaccine.

Saying that, it's now a known cause of blood clotting in some recipients: https://www.science.org/doi/10.1126/sciadv.abl8213

"chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 5 (HAd-V-C5) and human adenovirus type 26 (HAdV-D26) — the scientists found that ChAdOx1 had a strong negative charge, which meant that it attracted PF4, which has a positive charge."

We should also see how subunit protein vaccines such as Novavax will perform once they are widely available. From what it looks they should be equally effective and more anti-vaxxer friendly.

Most of the time and cost is associated with the trials - not the actual development AFAIK.

What would be more promising is if MRNA proves to be much more likely to pass trials. I think we need a lot more attempts at different viruses to have an idea here.

Certainly - if this HIV vaccine /does/ work - that's a huge win for MRNA.

> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine.

This is nonsense. The traditional vaccines don't work any better. They're worse. This is evidence MRNA is better than traditional vaccines.

Didn’t say they were. Rather that mRNA don’t seem to be approved faster for the new variants.

> This is evidence MRNA is better than traditional vaccines.

Haven’t been following the field that closely. I only seen one pre-print(probably Hungary?) where Sputnik was on par. Would love to see data if you’re willing to share.

Edit: I admit I’m a bit confused since I mixed “traditional vaccines” and Sputnik/AZ together. The latter aren’t traditional since adenovirus-based vaccines haven’t been previously deployed, same as mRNA vaccines.

I think there are -- they just haven't made it through the trials and approval processes yet. These are press releases from Pfizer for whatever it's worth:

Omicron: https://www.pfizer.com/news/press-release/press-release-deta...

Mentions delta: https://cdn.pfizer.com/pfizercom/2021-07/Delta_Variant_Study...

As I understood it, the actual vaccine was developed super quickly and then everybody waited for the results of the study.

Regulatory bodies need to adjust to the new speed of mRNA vaccine production if we want that sort of release schedule.

It took 2 days to develop the vaccine. https://nymag.com/intelligencer/amp/2020/12/moderna-covid-19...

1. The same mechanism of deliver is used so it's already tested and know to be safe/effective.

2. It replicates the same protein(s) found on the virus. So it will not due more damage than getting the virus and it will have a high probability of being effective.

No, the slow part is the efficacy testing.

Is this a problem with mRNA, a problem with the approval-for-vaccine-variants process, a problem with funding, or a problem with the politicians who thought COVID would magically go away by August 2021 (Never mind that most of the world was nowhere close to being vaccinated, and the millions of sick people throughout it were happily producing variants)?

I am ignorant on most of these subjects, but I would be surprised if the mRNA part of that was the problem!

if you mean "Developing mRNA vaccines from nothing to a working product" then yes, that's taken decades.

I don't really think that fact has much to say about if when you're already making millions of doses of commercial mRNA vaccines around the world this year, how fast next year's version can be made, tested, approved, manufactured at scale and deployed. The challenges involved seem to non-overlapping.

"delta- and omicron-specific vaccines" are coming soon, but this is still the very early days on mRNA vaccines, as a commercial mass-scale product.

Omicron has only been discovered in November and booster trials are still ongoing.

There are about 5 different false assertions in here with nothing to back them up.

The Israelis have found that a 4th shot isn't particularly useful in immocompetent healthy younger adults under 65. We're unlikely to have a 4th shot. This makes sense because in between the first dose(s) and the booster shot the immune system had time for the response to mature via hypermutation/maturation.

There's nothing wrong with the mRNA vaccines either since they're better for this virus than any other vaccine for this virus. The old school inactivate virus vaccines are worse than mRNA vaccines (although cheaper and easier to mass produce).

People compare mRNA vaccines to the polio vaccine but that is apples and oranges, since coronavirus is a virus that doesn't typically have a viremic phase (outside of severe multi-organ COVID). An appropriate comparison would be between coronavirus vaccines and flu vaccines. Comparing a coronavirus vaccine to a polio vaccine is just ignorant.

The mRNA vaccines are also wildly successful by the measure which matters most, which is protection against severe disease and death. They were never promised as being perfect against contracting the disease and transmission. You can lookup very public headline statements from Fauci in late 2020 before the vaccine trials were done setting expectations around a 50% vaccine efficacy against contracting disease.

We're also unlikely to be chasing after reformulating the vaccine for specific variants since by the time it could be updated and a hundred million doses were produced and shipped and we tried to get them into people's arms the variant wave would be over in that region. Just producing and moving the doses is a logistics problem that will take months. And the boosted response to the ancestral virus is still very strong against Omicron, and there's no evidence of any waning of efficacy against severe disease or hospitalization and no evidence of escape from T-cells (and the pattern of mutations in Omicron is random with respect to T-cell epitopes and shows no clustering).

The newspapers never should have sold vaccines as a way to stop the virus in its tracks. That isn't a problem with the science or the technology though. That is just that human emotions got out of control wishing for a magic shot that would make it all stop.

People often complain about the trials being cut short, but in fact we had enough data to determine the efficacy and safety outcomes. What we cut short was durability. Turns out the neutralizing antibodies and efficacy against infection/disease wane over 6-12 months (as it does with natural infection as well). That's the reason why the original 90% VE against infection numbers turned out to be wrong, we cut the studies short to start getting it into arms. The 90% VE against hospitalization/death have been maintained though.

> The newspapers never should have sold vaccines as a way to stop the virus in its tracks.

Which newspapers? It's easy to take shots at 'the media' (or equivalent).

Might have included a certain cardiologist on Twitter, but the notion is out there somehow and it didn't come from the scientists who know what they were talking about.