Maybe? The nice thing about mRNA vaccines is that the formula can be adjusted very rapidly (weeks). I feel like if there was a way to tweak the formula fast enough, we could react as fast as the different viral strains mutate. We would need to change the regulatory framework though. Having to do 3 phases of clinical trial involving tens of thousands of participants makes it hard to adapt fast enough.

doesn't the regulatory framework allow such changes though? afaik we aren't doing any phase 3 trials for the annual flu shot, or are we? (genuine question) But if we aren't, couldn't we just expand this to also take into account the Covid-shot?

The flu shot gets a special exception to the process. They study safety every year, but not effectiveness. This takes months off the development time.

> we could react as fast as the different viral strains mutate

The number of mutations is proportional to the number of people currently infected. The faster the virus spreads the more variants will be created. The fact that the N501 variant spreads faster seems to imply that the rate of mutations is already in the process of accelerating.

It may make more sense to use evolutionary modeling and analysis of existing SARS-type viruses to create antigens robust to all expected mutations. Here’s one such bit of research: https://www.biorxiv.org/content/10.1101/2020.11.17.387092v2

Is the risk that’s being assessed by these trials coming from the delivery method of the vaccine? Perhaps maybe there’s a way to get around some of those regulations.

So we will see weekly news about new strains and new vaccines to prevent them from spreading. This might be a long drawn process.

That's what BioNTech has been researching for years. BNT162b2 is, slightly exaggerated, a by-product.

From https://en.wikipedia.org/wiki/BioNTech:

It develops pharmaceutical candidates based on messenger ribonucleic acid (mRNA) for use as individualized cancer immunotherapies, as vaccines against infectious diseases and as protein replacement therapies for rare diseases, and also engineered cell therapy, novel antibodies and small molecule immunomodulators as treatment options for cancer.

HIV is hard as it attacks the very immune cells that come to get it.

It's not just that. People do develop neutralizing antibodies against HIV.

HIV, like other retroviruses, embedds itself in the cell DNA.

Some cells remain dormant for weeks and then start producing virions.

So the other problem with HIV, even if it didn't attack immune cells, is the hidden virus reservoir, I guess, just like other incurable viruses, like herpes and some hepatitis.

CRISPR can edit herpes simplex virus out of cells, so maybe it can do the same for HIV.

https://www.globenewswire.com/news-release/2019/11/18/194889...

Wow, thanks, that's really interesting!

Right but if you're vaccinated, you'd hope the immune system could attack HIV before it could take hold.

I really don't know enough about immunology to answer that -- but I presume most neutralizing antibodies wane over time.

If you take antiretrovirals you're very unlikely to become infected with HIV, even if you take it after initial exposure (but do your own research on that), but as soon as you stop, you lose that protection -- same with antibodies (not sure how a vaccine would help T-cell immunity if HIV infects T-cells).

While this is indeed a new vaccine modality, it doesn't change the dynamics of vaccinology appreciably. Things that were challenging vaccine targets in the past will likely remain challenging.

Doesn't it change the dynamics insofar as that you have a straightforward path from virus -> its mRNA blueprint, without more specialized and likely costly engineering of e.g. a adenovirus? This should then allow for broader protection against viruses with many strains e.g. a HPV vaccine cocktail that protects against all ~100 known strains vs. just the 9 it currently does.

Some influenza antibodies destroy certain neurons in your brain and you develop narcolepsy.

This is both true for natural infection and first generation vacines.

Later generation vaccines avoid this by not presenting certain proteins.

My point is, you can't just include hundreds of protein variants without a lot of trials.

I'm not suggesting to include new strains on the fly while they are discovered without trials. The same way they had to do trials for Gardasil-9 after already having Gardasil, they could do the same just with a wider cocktail.

In the optimal case you would attempt the 100+ cocktail and don't have any unreasonable side effects from them. Of course if there is a single variant in there that causes side effects you would need a ton of trials to triangulate which one causes them, but there is no guarantee that that is necessary or that you wouldn't run into that variant when you just adding 5 new variants in an iteration.

Do you have a reference for this? It was my assumption too, reading about the Pandemrix vaccine, but I didn’t find any dependable references for this.

Even if he is wrong about how it works, because of the potential for unknowns they need to study it in a trial. There is a lot we don't know about biology.