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Comment by superkuh | Hacker News Reader

Excellent news but there's a translation error or misunderstanding in this article.

> The scientists are using yeast as a receptor-binding domain.

I think they must mean they're using yeast as the protein expression medium and encode the receptor binding domain of the spike protein (along with the rest of the spike?) with yeast-y promoters and base sequence preferences. I guess there's nothing on the spike protein that needs to be glycosylated so non-mammal cell culture works.

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I was reading about the mRNA approach recently and wondered why not just inject the spike protein itself? Why have our body make the protein instead? Does anyone here know? It's interesting to see that both approaches yield such good results, and the end result, triggering immune response to the spike, seems about the same.

That's what the Novavax vaccine does, but it's still in testing and approval stages (although the trials results for now look like it works fine). As far as I understand, part of the problem is finding a way to produce the correct protein efficiently.

> Why have our body make the protein instead?

Not so easy to make enough, and handle it just like every isolated biological molecule?

It's expensive and difficult to scale when you're trying to make millions of doses.

It boils down to the mRNA process being faster and more of a sure thing for a novel virus. I hope there are eventually many more effective protein based vaccines approved.

The problem with expressing your protein in some animal cell is that often times there are sugars that cells add to proteins and they differ by lifeform type. So the protein will end up shaped different in a yeast than in a animal cell. Additionally, growing in a third party host lifeform often leads to situations where you can't get it to grow in the host anymore because the virus changes.

The sure thing for a novel virus, as I understood, is an inactivated vaccine.

For everything else, you are never sure if the biotech tricks, with all their intricacies, will work in that individual case.

Well, you're sure to get something with an inactivated viral particle. But you're not sure to get a usefully efficient protection from exposure to it.

The problem with inactivated viral particles is the inactivation process, neccessarily, breaks the proteins and cause them to be liable to take up non-realistic shapes. When your immune system trains on the non-realistic shape the antibodies don't neutralize as well. See the sinovac inactivated sars-cov-2 vaccine for an example of this type of vaccine not working out (ie, <50% efficient).

There's nothing medically wrong with the approach, however protein based pharmaceuticals are slow and expensive to manufacture, which isn't ideal when you are trying to vaccinate millions of people, cheaply.

To manufacture a protein you need to create a genetically modified bacteria that contains the DNA for that protein, grow a large batch of this bacteria (which can be difficult at scale), and then break open the bacteria filter out all the other proteins and just keep the one you want.

This is why the mRNA is so elegant, it gives your body the instructions to manufacture the protein itself.

Great answer, thank you!

The mRNA vaccines are sliced out of plasmids grown in bacteria (as DNA which is then transcribed into RNA).

https://www.nytimes.com/interactive/2021/health/pfizer-coron...

The nice thing about mRNA vaccines is that this has to be done only infrequently. The crucial point is that this DNA should be able to be transcribed into many mRNA molecules. Else, I have no idea how the one plant where the DNA is grown could supply the whole world.

The article I link implies they use each bottle of DNA in a day (not each batch, a bottle from the batch that they thaw for use).

I imagine it's a quality control thing.

The short answer is that proteins are too complex to manufacture, and it’s more effective to instruct your body (which has a lot of protein manufacturing capacity) to produce the protein.

There are attempts to use peptides. They are much shorter chains of amino acids , they are easy to produce, but it’s difficult to find peptides that reproduce the external structure of the virus. There is an experimental Russian vaccine based on peptides, but the results haven’t been published yet.

When the mRNA vaccine is injected into your arm muscles some of it ends up in the cells of the muscle and some of it ends up in the intercellular fluid. The latter drains via the lymphatic system and will end up in the lymph nodes in the upper body on the side you got the shot it (which is a good place to end up since the lymph nodes are a major site for immune response). Some will end up in the blood, and so might end up elsewhere.

Whatever cells it ends up in, the mRNA has them make the spike protein. That spike protein ends up attached to the outside surface of the cell that made it and it stays there [1].

If you injected spike protein directly, it could end up anywhere. I don't know if this has been tested in humans yet, but there has been research in mice where spike protein injected damaged their lungs [2].

[1] https://blogs.sciencemag.org/pipeline/archives/2021/05/04/sp...

[2] https://www.contagionlive.com/view/spike-protein-of-sars-cov...

Spike protein moving around free has been proposed as a potential source of the problems with the adenovirus vector vaccines.

(errors in the transcription process end up preventing it from properly attaching to the cell)

> will end up in the lymph nodes in the upper body on the side you got the shot in (which is a good place to end up since the lymph nodes are a major site for immune response)

Would it be worthwhile to get the first shot in the left shoulder and the second in the right shouder (or vice versa) so you have lymph node immune response from both sides of the upper body?

Aren't spike proteins moving freely, specifically, concentrating in the ovaries what is concerning Robert Malone? [1]

[1] https://bit.ly/2Td5gWz

E: curious why downvotes, am I misinformed?

No, they don't concentrate in the ovaries. That's choice morsel of bullshit antivax disinfo.

For a backgrounder of what actually happens, see Derek Lowe's recent blog[1]. Most of the lipid nanoparticles end up in the liver, which is exactly what you expect. There's a detailed debunk of the ovaries issue in [2].

Thanks for being curious about your part in spreading covid misinfo. I suspect most people aren't aware of what they're doing, just repeating stuff they heard from people they trust but probably shouldn't.

[1]: https://blogs.sciencemag.org/pipeline/archives/2021/05/04/sp...

[2]: https://byrambridle.com/

The talk I linked came out last week, they specifically discuss the articles you've linked.

Specifically, the reasoning your articles give for spike proteins being harmless is that they stay in the local injection site and lymphatic system. But we now know this is not the case and that these spike proteins do travel around the blood stream and concentrate in the ovaries.

The claims that guy made on the radio a while back were wrong but there is new information coming out about this and we specifically do not know the ramifications yet. Phizer is looking at the new data package right now.

At least, that is the argument currently being put forward, I don't know how much of it is fact based and how much is conjecture but it has me concerned at least somewhat.

Calling everyone an antivaxer really doesn't help anything. This shit is a moving target.

And you are not repeating stuff you read from other people? Details on safety and efficacy of vaccines for different sub-populations are still subject of study, new data is being generated, and as new information comes out, our ideas on the risks and benefits may keep changing.

Thank you for the links but please keep the arrogant tone down.

After vaccinating half the population, with the rate of discovered issues being hard to measure because it is almost background noise, the data is unlikely to substantially change for the other half of the population. PCPs already are aware of some subgroups that warrant additional caution and study, and additional study is ongoing to refine our knowledge. I would not classify that as expecting our understanding to change.

He linked to a meta analysis that links to many other studies to carefully support each statement. That is not the same as making claims that are not based in current data or statistics.

> the rate of discovered issues being hard to measure because it is almost background noise

Efficacy of post-vaccine follow-up and reporting may change with time, and hopefully will. The problem is that there is no meticulous data gathering from all vaccinated persons. Reports of issues are voluntary in most cases and in some cases institutions are not even notified by the vaccinated persons.

According to one study of VAERS frmo 2020, a passive reporting system, the real amount of issues is underreported; depending on the effect, the reporting efficacy is somewhere between 12-76% [1]. This is not a great system and because of that data gathering is not as fast as could be.

[1] https://pubmed.ncbi.nlm.nih.gov/33039207/

That is what I meant to say also.

So not to beat a dead horse, but there is no meticulous data gathering from unvaccinated people either, and we know that also suffers from vast underreporting. The one data set (being unvaccinated) simply also has a very strong signal of known serious health issues, while the other data set (getting almost any current vaccination) has a very weak signal of very rare, usually minor issues.

> If you injected spike protein directly, it could end up anywhere. I don't know if this has been tested in humans yet

Isn't that what the Novavax vaccine does? I'm not a medicine expert by any means, but my understanding from press reports was that they inject the spike protein directly (possibly attached to some substrate protein to carry it along).

https://en.wikipedia.org/wiki/Novavax_COVID-19_vaccine

Practical reason is that life sci VCs want to fund “platforms” in recent years, and mRNA can be pitched as a “platform,” so that’s what got funded.

One of the big reasons is that mrna is also much easier to manufacture than proteins. If I wanted to, I could pay for a arbitrary mrna sequence delivered to be within the week. Its basically been commoditized.

Conversely, getting a protein at scale requires the engineering of an organism to synthesise the protein of interest. This results in increased delay in manufacture.

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