mRNA vaccines – a new era in vaccinology (2018)

I got the Pfizer vaccine.

This is such a huge step from some of our older vaccines, which had much higher side effect rates, relatively speaking. These vaccines were tested in large clinical trials, and we're seeing very few poor outcomes. And yeah, what's in this vaccine is so much more ephemeral than "This virus is...mostly harmless?"

I'm not suggesting that the vaccines could do the same, but it's not that big of a leap to wonder if the virus can retranspose, then the vaccine could as well.

Also I'm aware it's a preprint and not fully peer-reviewed yet, interesting nonetheless.

https://pubmed.ncbi.nlm.nih.gov/33330870/

The risk profiles in either direction are so small it’s very hard to discern a meaningful pattern. It probably just doesn’t matter at all what you do.

Most variation between populations is not so much what genes are there, but how at what level they are expressed, point mutations, and short repeats (all of which are unlikely to create totally new structures). For there to be a population that had spike protein expressed, there would have to have been some sort of horizontal gene transfer into the germline (which is relatively protected from mutations for precisely this reason) at some point in the past. There’s reasonable atlases of human genetic variation (see, for example, the 1000 genomes project), so if there was some large population of people with any obviously new viral sequence, we’d see it.

Plus, if a person somehow, miraculously, had a protein that looked like Spike, their immune system should already be tuned to ignore it. (I have a PhD in biology, but immunology was not something I have much expertise in, so take this with a grain of NaCl).

This whole pandemic I've been waiting for us to "get lucky" and find that the virus has some weakness. Like some simple off-the-shelf medicine is a cure. Or that it spreads through some simple mechanism we can beat easily. Or that it can't handle summer. Or that it would never mutate.

Nothing seemed to go our way though.

Then the mRNA vaccines came and that was finally our lucky break! Now thanks to this article I can see that the real breakthroughs came years earlier, from basic researchers. Without these breakthroughs -- which I'm sure didn't excite the public or earn anyone a Nobel prize -- we'd have only inferior vaccines out there.

Anecdotally, I have a very elderly acquaintance that reacted quite poorly to the vaccine, including developing "shingles" in her eye. A nurse taking care of her then accidentally exposed her to COVID, which she subsequently tested positive for but had no symptoms.

Seems that you live in North America. It is utterly bewildering that people are expected to make this determination.

I can go to the ER whenever I suspect a serious problem, to the ultimate cost of... 5 euros. That's the limit. Post-occupation EU backwater country.

It's not peer reviewed yet but here is this:https://www.medrxiv.org/content/10.1101/2021.03.05.21252960v... Evidence of the spike protein by itself causing clotting issues.

Not if they were long-term effects that took 1-2 years+ to manifest.

Most likely. SARS-CoV-2 is now endemic in the human population & unlikely to die out. The general impression in the scientific community is that the current set of vaccines should be protective for at least a year or two, at which point variants will have emerged that evade the vaccines developed on the Wuhan strain. Booster shots developed on these new variants would be required for the foreseeable future.

> Or something a bit more reactive where it is possible to get a shot after infected or having symptoms and whether mRNA works in this way as well on a reactive basis.

In principle this is possible - some vaccines are capable of arresting an active infection, though that is highly specific to certain pathogens. This is not something current COVID vaccines can do.

This was the first large-scale use of this kind of vaccine so it is an amazing field test of the process. Normally that would be a slower, incremental process but the risk from Covid forced them to simplify and speed up the process.

Not toxic directly. Disrupting "good" bacteria that we co-exist with isn't always harm free, as I'm sure the people researching those polymers are well aware of.

With antibiotics, they are very broad spectrum so you can throw augmentin at routine infections and it'll usually work.

With phages, you have to be much more specific. Phage X for bacteria Y. It's not necessarily hard figure out what bacteria it is, but it takes time and expensive lab work.

Much harder to identify the misbehaving cells, DNA deletions, than making all cells behave, I assume.

I don't know why this evoked such a negative response. I will just cool off posting comments on HN for a while.

Many moons ago, when I lived in a community where most residents were of the all-organic-no-vax types, I convinced the powers that be that vaccination was a moral obligation for the (mostly young) community due to the effects of infecting young and old and the resulting deaths.

Everyone got a flu vaccine that year. I was not very popular after that ;(

No? Newton? Pascal? Lemaitre? Wheeler?

It may be that the vaccines will be incapable of giving us herd immunity, but they may allow us to keep the R number below 1 with much less extreme social distancing and lockdown procedures.

Without the vaccines, the only way to get rid of this pandemic is through severe economy-damaging lockdowns and liberty-encroaching contact tracing and quarantining. If we can achieve the same thing with vaccines plus just having to wear a mask when near other people, then I would say that vaccination would still be a moral obligation, even though we haven't achieved herd immunity.

It's a tremendous breakthrough, I'd say. But rather than focus on the tech, I'd rather see a rethinking of our governmental approach to issues concerning public health and how approval processes are set up. I'd rather focus on how we incentivize breakthroughs on issues that are most important, rather than developing another medicine that's 1% better at treating acne, for example. And I'd rather see cultural changes around adopting already existing technologies -- less than half of folks take flu shots!

I'd argue that getting flu shot numbers way up would be more of a breakthrough than any benefits from mRNA, as incredible as it is. Not that we have to choose one or the other. I'm just saying I'd like these other issues to get more prominence.

It's also why I'm incensed that vaccine production is ramping up both too slowly, and will top out at too low a number. It can't take six months to vaccinate the first world, and eighteen to vaccinate the developing world against a variant.

I get that sentiment. There's a question of alignment of incentives.

Covid19 vaccinations are likely to be a thing for many years to come, and there are a number of entities that will be able to produce those future vaccinations. If one of the big vaccine providers produces something that's demonstrably less safe than the others, then the odds of them getting more money for future vaccines goes down.

It's far from a perfect system, and there are a lot of holes, but in this case, things line up pretty well.

In short, you can be confident that these companies are primarily focused on long-term profit, which often aligns with good short and long term outcomes for its customers.

Oh, I'm with you on this, but I think it's only a matter of time before things get very uncomfortable.

In fact, instead of taking that vaccine shouldn't you give it to a school teacher or hospital worker in a country that doesn't yet have the vaccine?

This 'moral obligation' nonsense sounds good at face value but really doesn't hold up in practice.