We got what's needed for COVID-19 vaccination completely wrong

by ChristianKl5 min read10th Feb 202132 comments

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Covid-19
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I would summarize the leading thought in 2020 on vaccination on LessWrong and the review that's now popular in the mainstream as:

New vaccination technology like mRNA-based vaccines and adenovirus-based vaccines allow faster development of vaccines. We still have the challenge of building enough vaccine factories. To build enough vaccine factories.

This seems to be wrong and the better view is:

Peptide-based vaccines are well understood and unsexy. We have existing adjuvants with well understood safety profile. They can be easily produced with equipment we already have. Given that they are unsexy nobody wants to run a clinical trial right and Western governments are interested in suing people for developing such technology then they are interested in vaccine development.

According to it's Moderna's information, the first patient who got the Moderna vaccine got it on the March 16. Two weeks later Euroimmun founder and biotech billionaire Winfried Stöcker gave himself the first dose of a vaccine he developed himself. In contrast to Moderna he however was not focused on bringing a vaccine to market. He just wanted don't wanted to get COVID-19 and vaccinated himself. His company rather focused on developing antibody tests that were in short supply at the time.

Given past studies of the Coronavirus it was common knowledge that targeting the spike protein of COVID-19 was a good idea for developing a vaccine. Moderna announced that they designed a vaccine in one day by simply targeting the spike protein. Stöcker decided to also go for a domain of the spike protein and mixed it with an already well-understood adjuvant. Given that a lot of the risks from a vaccine come from bad adjuvants and he thought that being in his 70ths getting COVID-19 was undesirable the risk calculation clearly came out in favor of vaccinating himself with his mix. After everything went well with himself and he developed antibodies as predicted he blogged about it and gave it to his family as he didn't want them to get COVID-19 either.

It's hard to get the timeline right here but Preston Estep, Don Wang, Alex Hoekstra, Ranjan Ahuja and George Church et al had a similar idea. They also didn't want to get COVID-19 and knew plenty about biology. In contrast to Stöcker they cared a bit more about not being boring and thought about what they wanted out of a vaccine and coordinated with their friends instead of just making a vaccine alone for themselves. They wanted something that's easy to brew together and that still works even if the spike protein mutates. Instead of just targeting a protein domain of the spike protein they focused on nanopeptides that are shorter sequences then individual protein domains. Short peptides also have the advantage that they are easy to order online instead of having to wait 1-2 weeks for a protein domain like the one targeted by Stöcker it's a matter of days to get the sequences one orders for short peptides.

They brew together RadVac and decided to make their whitepaper public in late July where the first public version of the whitepaper seems to be version 2-3-2 from the July 29, 2020. That's the kind of version number one usually sees in software projects. While the FDA would never allow a product that's developed as agile to be sold, publishing information is free and given that no scheduled substances are involved in RadVac people are free to brew RadVac together for themselves.

Sometime in September Stöcker thinks (not his words):

"It seems like the commercial vaccine trials don't provide us a vaccine that allows us to vaccinate everyone in Germany this year. I could easily brew up enough vaccine doses so that we could vaccinate everybody in Germany this year and give them antibodies."

Stöcker then writes the Paul-Ehrlich-Institut (PEI), which is the German institution responsible for vaccination, a letter proposing to vaccinate everybody in Germany who wants by the end of the year based on his experience of giving five probands (including himself) his vaccine nobody having side-effects and all developing antibodies. First giving it to a sizeable number of volunteers and then giving it to even more volunteers. A single 2000-liter-reactor is able to produce enough peptides for vaccines for 1 million people per day.

From the perspective of the PEI this is heresy. They first ignore his letter and then contact another agency to sue Stöcker for making an unregistered clinical trial with his five probands. By German law as a doctor who's allowed to practice medicine, Stöcker is allowed to give his patients a mix that he brew together medical trials require registration. In an actual trial with 64 patients Stöcker finds that the adverse reactions to his vaccine brew are a lot lower then that of the currently approved vaccines with their new technologies.

It's worth noting here that the side-effects of the existing vaccines are worth enduring to be protected against COVID-19. I just want a vaccine and if that means I'm ill for a day because of an adverse reaction that's completely worth it to be protected against COVID-19. For this post I will leave the question of why companies pushed for getting the new technology to market here for the reader.

Zvi wrote that the problem with the Gates Foundation was that they didn't trust the new vaccination technologies enough. The problem seems to me the polar opposite. They fall for the mRNA researchers conning them when they funded them via CEPI. The mRNA technology seems to provide no benefit over simply giving the peptides directly but the mRNA researchers really wanted to do fancy research on mRNA.

Gates had a model where he could simply give the mRNA people a few billions to build the necessary factories to produce the vaccines in a time of crisis like our pandemic. Zvi also seems to think this to be true. From basic EA principles we know that room for funding is central when it comes to effective charity interventions. As LessWrongers we understand programming and the principle of the Mythical Man-Month where adding more programmers to a project doesn't always make it faster. Chief Financial Officer and Chief Operating Officer of BioNTech Sierk Poetting is on record (DER SPIEGEL Nr. 6 / 6. 2. 2021 Site 64) for saying that there was open room for funding for their vaccine effort in 2020. Given that Moderna's vaccination effort got a similar amount of funding as that of BioNTech/Pfizer, I would expect them also to have no open room for funding. Mixing the mRNA with their lipid coating seems to require custom microfluid mixing technology that can't be simply ordered and where scaling up the production needs more then just money.

After hearing from Michael Vassar last year that we need a truth and reconciliation committee after this is over, I'm at the point where I want a truth and reconciliation committee.

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I think this might be (very slightly) unfair to mRNA vaccines, as the comparison between them and peptide vaccines is pretty situation dependent:

  • We have reason to believe that peptide vaccines will work particularly well here, because we're targeting a respiratory infection, and the peptide vaccine delivery mechanism targets respiratory tissue instead of blood.
  • That said, mRNA vaccines are expected to elicit much stronger immune responses than peptide vaccines would.
  • I suspect that the low efficacy of mRNA vaccines (only 95% - low is relative) is likely because they're only targeting the spike protein, which apparently has 'high mutant escape potential'.  We have a LOT more information about the virus now than we did when the mRNA designs were finalized.  If companies had been allowed to make mRNA vaccine updates without resetting all the clinical trials, I believe we'd have a substantially better/stronger vaccine than just 95%, with a single shot instead of two.
  • mRNA vaccines are really just a technology demo at this point; sure, you can make vaccines with the tech, but that's not the real superpower here.  The superpower is that we have a platform we can use to generate arbitrary proteins in live cells, including proteins we know about but for which we have no reasonable delivery mechanism.  Not all proteins/peptides are water soluble, and fewer are able to get through cell walls.
  • As a technology demo (and not a simple one at that), it's surprising that companies have as much production capability as they do.  I would expect that capacity to be ramped up substantially in the next few years as we start aggressively making use of mRNA treatments to address a host of issues.

To sum up, my view is that mRNA technology is pretty great and I'm really, really glad someone was able to make use of the disaster that was 2021 to ram through safety and clinical trials. My issue is less with the technology and it's large promise, and more with how vaccine testing and rollout has been botched or unnecessarily slowed down at every level.

Peptide vaccines are easy and fast to both design and construct, while being safe unless you really screw up, and effective as long as designed correctly.  However, they do have rather substantial limitations, and it's just happenstance that they're particularly well suited for the situation.  I could see mRNA vaccines having a much wider berth.

We have reason to believe that peptide vaccines will work particularly well here, because we're targeting a respiratory infection, and the peptide vaccine delivery mechanism targets respiratory tissue instead of blood.

Just a minor point: by delivery mechanism, are you talking about inserting the peptides through the nose à la RadVac? If I understand correctly, Werner Stöcker injects his peptide-based vaccine.

I suspect that the low efficacy of mRNA vaccines (only 95% - low is relative) is likely because they're only targeting the spike protein, which apparently has 'high mutant escape potential'.  We have a LOT more information about the virus now than we did when the mRNA designs were finalized.  If companies had been allowed to make mRNA vaccine updates without resetting all the clinical trials, I believe we'd have a substantially better/stronger vaccine than just 95%, with a single shot instead of two.

Eh, I guess I'm skeptical that it's that easy, even now, to make changes to the mRNA vaccines that would bring us from 95% up to 100% protection (against symptomatic infection), without knowing more about what's happening to that 5%. The spike protein does have "high mutant escape potential" as we are seeing, but I'm not sure that's what's behind 95% vs. 100% efficacy, given that the clinical trial data was gathered mostly before mutants really started taking off. It could just be inherent variability in the strength of people's immune systems. Not that it matters a ton, it's not like those 5% are developing severe disease, and given that I think it's weird to call the efficacy low (even in a relative sense — relative to which more effective vaccines?).

I should probably know this, but are any of the mass produced COVID vaccines peptide vaccines?

The Novavax candidate is a recombinant protein.

I don't believe so, only radvac and euroimmun are peptide based. My question is why none of the commercial vaccines are peptide based (?) given this is a very well established vaccine technology (and particularly well suited for sars-cov2. 

My issue is less with the technology and it's large promise, and more with how vaccine testing and rollout has been botched or unnecessarily slowed down at every level.

I agree that the main issue is regulation that makes vaccine testing and the rollout harder then it needs to be.

We don't know at this point how often you can give someone polyethylenglycol-based mRNA without their body creating a serious allergic reaction against it. That's an open safety question that needs to be addressed before you can use mRNA treatments to address a host of different issues. We already have substantially more side effects for the second vaccine dose then the first.

The evidence that the adenovirus-based and mRNA-based vaccines are safe and effective is large-scale trials with tens of thousands of participants.

The evidence that Stöcker's peptide-based vaccine is safe and effective is Stöcker's own testimony that he and a few other people used it, didn't get sick, and have the relevant antibodies. [EDITED to add:] Sorry, "a few" isn't fair because he claims to have done a further experiment with 64 people. ~70 people is definitely better evidence than ~5 people, but I don't see any reason to trust Stöcker enough to be confident that what he says about those ~70 people is actually true.

The evidence that RadVac is safe and effective is a general argument that it should be safe and might be effective, and so far as I can tell nothing else at all.

It might be true that the peptide approach is better, but I'd want to see much better evidence before calling for a "Truth and Reconciliation Committee" to look into the alleged awful misdeeds of the people who promoted other approaches.

The evidence that Stöcker's peptide-based vaccine is safe and effective is Stöcker's own testimony that he and a few other people used it, didn't get sick, and have the relevant antibodies.

"Truth and Reconciliation Committee" to look into the alleged awful misdeeds of the people who promoted other approaches.

I don't think promoting other approaches is the problem. The problem is suppressing certain efforts that are helpful. If the RKI would have cooperated with Stöcker I would have now relevant antibodies because I would be vaccinated. 

I don't fault Moderna, BioNTech for what they did in 2020 but I consider the actions of the regulatory agencies worth "Truth and Reconciliation Committee" as they prevented us from fighting the pandemic effectively.

The evidence that RadVac is safe and effective is a general argument that it should be safe and might be effective, and so far as I can tell nothing else at all.

This is a funny sentence. Basically it's saying that if we see the most informed people doing X then that's no evidence that doing X is a good thing to do. You likely wouldn't make that argument in any other context but here the dogma is strong enough that people could think this is no evidence. It's like "there's no evidence for mask working for the average person" when there were no studies for that last year.

It seems to be that there's a fine line between what RaDVaC is doing in their communication about their vaccine and what Stöker is doing and when you are over that line you get persecuted by the government. 

I expect that RaDVaC is very careful about not providing legal attack surface and providing other kinds of evidence could be seem as illegal product advertisement. 

What do you mean by "suppressing"?

I know of one instance of attempted suppression: Stöcker gave his alleged vaccine to a bunch of people and someone brought a legal action against him for running an unregistered clinical trial.

If that's what you mean: it seems to me that if someone breaks the law, then taking the legal steps that are generally taken against people who break the law isn't obviously properly described as "suppressing his efforts", even if he claims he did it for the Greater Good. (It sounds as if you reckon he didn't break the law because he's a doctor; maybe you're right -- I don't know anything about German law -- but it seems to me unlikely that anyone would bother making laws against unregistered clinical trials if you could work around them simply by having a doctor administer the drugs, since surely that happens in pretty much all clinical trials anyway, and I've got to assume that whoever brought the case against Stöcker has some idea what the law says.)

If instead you mean that the German agencies didn't actively work with Stöcker to bring his alleged vaccine to proper clinical trials, mass production, etc., then again it seems to me that this doesn't deserve the name of "suppression". I bet there are thousands of people claiming to have better ways to deal with COVID-19, and I bet they're all writing to institutions like the PEI demanding that things be done their way. What algorithm are you proposing they should have executed that would have told them to put time and effort into working with Stöcker but not with dozens of cranks? And how are you so sure that Stöcker isn't a crank himself? Again, so far as I can tell we have only his word for it that his alleged vaccine is safe and effective, even on the small sample of people he allegedly tested it on.

Basically it's saying that if we see the most informed people doing X then that's no evidence that doing X is a good thing to do.

If "basically "means "not", I guess. I don't see much connection between what I actually said and what you say I "basically" said.

If you mean that in addition to the RadVac folks' general argument that their alleged vaccine should be safe and effective, the fact that they have chosen to actually take it is a little bit more evidence, then I guess I agree: but (obviously, I think?) it's not much further evidence. (It tells me that they probably find their own arguments convincing, which isn't exactly a surprise.) And I don't see any obvious reason why I should consider the RadVac folks "the most informed people".

If that's what you mean: it seems to me that if someone breaks the law, then taking the legal steps that are generally taken against people who break the law isn't obviously properly described as "suppressing his efforts",

Of course laws are supressing people from engaging in certain actions whether or not those laws are desirable laws, laws are supressing. 

In this case, it seems that while it's completely legal for a doctor to brew anything together and give it to their patients it's not legal to run a clinical trial without registration.

If RaDVaC folks would publish the evidence that they gathered for their vaccine it's easy to argue that they did run a clinical trial for the vaccine which they seems to desire to avoid. Given that they are not allowed to provide that kind of evidence publically they have to be Straussian about it.  

it seems to me unlikely that anyone would bother making laws against unregistered clinical trials if you could work around them simply by having a doctor administer the drugs

There's a difference between having a doctor administering the drugs and being a doctor administring drugs. Doctors are allowed to give their patient any brew they make but there are rules that regulate the conditions under which you can give a brew to a doctor to administer to his patients. There are some rules that regulate what doctors can do with scheduled substances but those aren't applicable here. 

Secondly, rules for Phase I clinical trials exist for protecting clinical trial participants. They don't exist to prevent people from doing experiments on themselves and their family. 

Saying that a doctor who brews a vaccine for themselves in March and give it to a total of five people he cares about before September is engaged in doing a clinical trial seems to me like a huge stretch.

What algorithm are you proposing they should have executed that would have told them to put time and effort into working with Stöcker but not with dozens of cranks? 

If you have a pandemic and a biotech billionaire contacts you with wanting to help you treat him different then dozens of cranks that also want to contact you. Especially if the company they founded helps you with fighting the pandemic (they provide COVID-19 tests). 

If you mean that in addition to the RadVac folks' general argument that their alleged vaccine should be safe and effective, the fact that they have chosen to actually take it is a little bit more evidence, then I guess I agree: but (obviously, I think?) it's not much further evidence. 

Skin in the game is a good way to handle problems of information assymetry and trusting expertise. 

Just because a drug is FDA approved doesn't mean that it has an effect or is safe either.  If I saw a FDA official or a Ranbaxy employee telling his doctor to make sure that he gets a brand name drug instead of one from Ranbaxy you can take that as good evidence that made you shouldn't trust the FDA approved Ranbaxy drug. 

The question here is whether general arguments that experts make based on inference are reliable, or do you need specific evidence. What is the track record for expert inferences about vaccines?

From a quick search, it seems that the clinical trial success rate for vaccines is about 33%, which is significantly higher than for medical trials in general, but still not all that high? Perhaps there is a better estimate for this.

Estimation of clinical trial success rates and related parameters https://academic.oup.com/biostatistics/article/20/2/273/4817524

The mRNA technology seems to provide no benefit over simply giving the peptides directly but the mRNA researchers really wanted to do fancy research on mRNA.

I think you're giving mRNA vaccines too little credit and peptide-based vaccines too much.* I haven't looked into peptide vaccines much at all but my general impression is that they don't work that well as a class. Hundreds of peptide vaccines have entered the clinic with no approvals (albeit, not all against infectious diseases, many against cancer which is more difficult) — without looking into the details, I couldn't tell you exactly why, but my guess would be lack of efficacy. When you present something to the immune system, it's important that it be in the right shape so that it trains the immune system properly. Peptides, removed from the context of the protein scaffold that they are normally a part of, are very floppy, and there's no guarantee that the conformation a peptide takes will be the same as the conformation it takes in the native protein (more precisely, probably some of the conformations the peptide takes will be similar to the conformations in the native protein, but how many other conformations will the peptide be taking that are dissimilar, and will steer the immune system the wrong way?). A good heuristic is that to have an effective vaccine, you want to present something to the immune system that's "as close to the real thing" as possible. mRNA vaccines, by being compatible with presentation of a full viral protein, allow you to do that. Peptide-based vaccines, less so.

*It's worth noting that mRNA vs. peptide is a bit of a weird distinction, since mRNA is just a delivery mechanism, and so is also compatible with delivering peptides if that's the way you wanted to go.

Proteins are peptides. When you give whole-proteins, protein domains or nanopeptides (short peptides). With peptide vaccine I mean a vaccine that contains peptides opposed to one that contains mRNA.

A good heuristic is that to have an effective vaccine, you want to present something to the immune system that's "as close to the real thing" as possible. 

That leaves the question of what "as close to the real thing" means. We have multiple usecases like an universal flu vaccine where the goal is to get the body to develop antibodies precisely against those sections of proteins of the flu virus that are conserved and don't change year to year.

Peptides, removed from the context of the protein scaffold that they are normally a part of, are very floppy, and there's no guarantee that the conformation a peptide takes will be the same as the conformation it takes in the native protein 

MHC proteins don't take native proteins. They take short peptides. If the short peptide doesn't naturally fold in the same way as it folds in the native protein I don't see how the human immune system would manage to build effective antibodies. 

There are peptides in the RaDVaC vaccine where they created short peptides that fold into the shape of that the native protein has but that's a different shape then you get if you just take the subsequence of the native protein and let it fold. 

I think this leaves a lot of room for ambitious projects like a universal flu vaccine or a HIV vaccine that achieves better results then our bodies to naturally that then can fail their goals in clinical trials. 

mRNA is just a delivery mechanism

Yes, the thing that's making the effect is the synthesized peptide. I wrote the above with the assumption that you can generally give that protein directly. Just synthesise it and inject it.

Proteins are peptides. When you give whole-proteins, protein domains or nanopeptides (short peptides). With peptide vaccine I mean a vaccine that contains peptides opposed to one that contains mRNA.

It's worth noting that calling proteins peptides is not standard terminology. If you say "peptide-based vaccines," it's generally understood that you're not including protein-based vaccines (also known as subunit vaccines). And in your original post, it does sound like you are making this distinction. If you aren't making this distinction, then it doesn't quite make sense to decry the lack of focus on "peptide-based vaccines" (including protein-based ones) as opposed to mRNA when there are plenty of protein-based candidates (most notably Novavax) in advanced clinical development.

ETA: Read more about Stöcker's vaccine; it's not a peptide-based vaccine, it's a protein subunit vaccine, using the whole RBD (peptides are usually <50 amino acids, the RBD is a couple hundred). So a different approach than RadVac. Just on priors I'd expect this to be more likely to work.

That leaves the question of what "as close to the real thing" means. We have multiple usecases like an universal flu vaccine where the goal is to get the body to develop antibodies precisely against those sections of proteins of the flu virus that are conserved and don't change year to year.

Yeah, that's fair — "as close to the real thing" isn't always the best (e.g., see inactivated or live attenuated vaccines, which have plenty of problems). But when comparing vaccines where a whole protein is presented (so subunit and mRNA) to peptide-based vaccines, I think the fact that the whole protein has a more native-like conformation is a huge advantage in favor of the former. In the example of universal flu vaccines, the most advanced candidates are all presenting whole protein domains, not peptides.

MHC proteins don't take native proteins. They take short peptides. If the short peptide doesn't naturally fold in the same way as it folds in the native protein I don't see how the human immune system would manage to build effective antibodies. 

Fair enough for MHC's, but this only holds for T cell-based immunity. B cells, on the other hand, absolutely care about the conformation of the protein as it exists. To build effective antibodies to whole proteins, the immune system selects for B cells that display antibodies that bind well to those whole protein targets (MHC's, and therefore peptides, are involved in this process as well, but that doesn't change the fact that the antibody displayed by the B cell still has to bind well to the whole protein in order for that B cell to be selected for). 

There are peptides in the RaDVaC vaccine where they created short peptides that fold into the shape of that the native protein has but that's a different shape then you get if you just take the subsequence of the native protein and let it fold. 

It's good that they're doing this (I skimmed the white paper and saw an example where they introduced a non-native disulfide bond), it's probably better than just using the native sequence for all their peptides. But I'd say our tools for this are pretty limited, and you're still going to end up with a crude approximation of the native fold rather than exactly the native fold, which is just better.

It's worth noting that calling proteins peptides is not standard terminology.

It's the terminology that you get when you read the dictionary whether cambridge or webster. I had my molecular biology lectures in German and more then a decade ago, and the German Wikipedia still sees the German word Peptide as having the dictionary definition it has in English.

I can see how it's can be confusing when peptide is usually meant for shorter strings.

It seems like we have problem in Wikidata with diverging German and English definitions for https://www.wikidata.org/wiki/Q172847 . What name would you use to talk about a chain of two or more amino acids?

But I'd say our tools for this are pretty limited, and you're still going to end up with a crude approximation of the native fold rather than exactly the native fold, which is just better.

I would expect that we have experimentally determined the structure of the native fold. I would expect that our computer models might be good enough to predict how an amino acid chain of <20 amino acids folds.

there are plenty of protein-based candidates (most notably Novavax) in advanced clinical development.

It seems good that CEPI funded them. I think the issue here is that Novavax doesn't have a vaccine on the market and has their own property adjuvant so it's not an "existing adjuvants with well understood safety profile" that you would want when skipping phase 3 trials. It also means there likely hasn't been large scale manufacturing of the adjuvants before which is also problematic. 

What name would you use to talk about a chain of two or more amino acids?

Yeah I don't know if there is a term that's not super clunky like "amino acid-based polymer." But I think the more fundamental issue is that it's weird to group peptide-based and protein-based vaccines together for the claims that you're making. You can't both fend off the claim that "whole protein domains are better immunogens than peptides because they have more native-like folds" by saying that "proteins ARE peptides, and are included in my category" AND say that "it's irresponsible for us as a society not to have invested more in peptide-based vaccines because they're so cheap and easy to synthesize", when "cheap and easy to synthesize" don't apply to protein-based vaccines.

I would expect that we have experimentally determined the structure of the native fold. I would expect that our computer models might be good enough to predict how an amino acid chain of <20 amino acids folds.

Yes, I would agree with both of those (although less sure about the second one, given that I'd expect a peptide of <20 amino acids to have an ensemble of conformations; it's one thing to be able to predict the lowest energy conformation, another to predict exactly what percentage of the population is in each of 20 possible conformations). But more importantly, it's difficult to bridge from one to the other. If you're starting with the original peptide sequence, the best you can do is probably introduce a disulfide bond or cyclize it to introduce some conformational constraint, but that's not going to constrain it the same way that the native scaffold would've. You could maybe do de novo computational design of the peptide (not starting with the native sequence) to have the desired fold, but that's more cutting-edge stuff and not what RadVac did, and I'm not sure how well that would work anyway.

when "cheap and easy to synthesize" don't apply to protein-based vaccines.

Why aren't proteins cheap to produce? You do CISPR on some hela cells and they will produce the proteins for you. I would expect that's what behinds Winfried Stöcker claim to be able to produce a lot of vaccine very cheaply very fast. 

(Side note: You wouldn't use CRISPR nor HeLa cells, but rather traditional cloning techniques + any of a number of other cell lines traditionally used for recombinant protein production. But that's tangential to your question.)

I'm far from an expert here, but anything involving cell culture is generally thought to be pretty expensive. The media is expensive, other culture conditions can add to the cost as well (e.g. continuous supply of CO2 for mammalian cells), transfection reagents are expensive, and you have to expend a lot of effort keeping out bacterial/fungal/viral contamination. The inherent variability in biological processes means that you have to deal with batch-to-batch variability in your recombinant protein product, which might mean added expenses in monitoring and analysis (and headaches dealing with regulatory agencies). Basically, cells are fickle and require a lot of babysitting and care.

mRNA vaccines don't have any of these issues, because cell culture isn't involved for the most part. Most everything is done in vitro — in that sense, mRNA vaccine production is more like chemistry than biology. And, therefore, it's more similar to peptide-based vaccine production (chemical synthesis) than protein-based vaccine production is — which, again, is why it's weird to contrast peptide- and protein-based vaccines together against mRNA vaccines.

Peptide vaccines aren't old and boring, they are new and unproven. From a 2014 review 

The vast majority of candidate peptide vaccines are under Phase I (270 studies) and Phase II (224 studies) stage of development.In a total of 452 studies, only 12 studies have progressed to Phase III level of development.Interestingly, all these 12 studies are on therapeutic candidate peptide vaccines indicated for treatment of multiple types of cancers.

AFAICT no peptide vaccine has ever been approved for human use.

So yes, maybe a peptide vaccine could have worked better, but it would have been as much an innovation as the mRNA vaccines.

[this just from googling right now, I'd never heard of peptide vaccines before]

I don't know about subtle difference between proteins and peptides, but I would say the relevant category is "recombinant vaccines" and I believe that the first such was the Hepatitis B vaccine approved in 1986. This used genetically engineered yeast to produce a protein from the virus that was harvested and injected into people. 

Novavax (non-mRNA) may be more effective on new variants. https://www.biospace.com/article/comparing-covid-19-vaccines-pfizer-biontech-moderna-astrazeneca-oxford-j-and-j-russia-s-sputnik-v/

Here is a specific proposal about the role of sexiness, ie, newness. I don't mean to put a lot of weight on this hypothesis as opposed to the general class, but it is useful to spell out details. Also, I'm not sure what you're saying and I suspect this is about a somewhat different irrationality than you were proposing.

Perhaps governments will not allow drug companies to profit in cash from selling vaccines. But they can still profit in intangible experience. This is most obvious with Moderna and BioNTech, whose existence is predicated on mRNA vaccines working in general and the companies being able to make them in particular. After this is over, they may not have any more net cash, but they will find it easier to raise money and convince regulators, not to mention that they will be more competent. Similarly, AZ and J&J will learn about vector vaccines.

I think a vaccine strategy that would have resulted in enough vaccines to vaccinate everyone at the end of 2020 would have been benefitial to a vaccine strategy that helps Moderna and BioNTech gather more experience with their technology platforms. 

I'm not arguing that giving Moderna experience with their technology platform isn't useful but it's not worth the delay in vaccination over using technology that can be more easily scalled up. 

Another technique would be to remove a vial of blood, add covid, keep the blood alive, and wait till it beats the covid. Then reinject blood full of trained immune cells.

Is this a thing? Why not? 

The vaccine by Stoecker is a protein subunit produced by cell culture. It uses cell machinery like ribosomes, and, more importantly, chaperones, which fold the polypeptide correctly, to make it a functional protein (or protein subunit in this case).

Unlike Radvac, which is a mix of peptide strings synthetised chemicaly.

Both share the feature that they are easily produced in large quantities while mRNA vaccines aren't.