Do the COVID-19 vaccines work differently than earlier vaccines? (mRNA)

My biology education was many years ago in high school so I have forgotten most of it. I have been reading though and I think I have the basics of how vaccines like Pfizer and Moderna work (mRNA).

My question is, it seems they have engineered mRNA to enter your cell and have it produce certain proteins which will render you immune to the COVID-19 virus.

Is this different than what was done before? I thought the way vaccines worked (or used to work) was you injected a weakened or inactive version of the virus and your body just saw it like any other viral infection. Your immune system would rally to fight the new infection and learn its ways which the body remembers for the future. If you get infected again your body is prepared and jumps on it before it has a chance to cause any trouble.

But now are we just telling the cells directly what to do? Does this mean the immune system has been trained Matrix-style to “know” what COVID-19 looks like? Actually, do the mRNA even engage the immune system or is it just telling your cells how to reject COVID-19 when it arrives so it can’t start replicating?

mRNA vaccines are indeed new. The COVID ones aren’t quite the first ones ever, but they’re certainly the first ones so widely deployed.

And they don’t give instructions to the immune system directly, like you’re imagining. The protein they code for is one of the proteins that makes up part of the coronavirus (specifically, those spikey things arranged around the outer surface). The immune system then reacts to those, the same way that it’d react to spike proteins found on a real virus.

I’ll admit that I’m not very clear on why this works better than just injecting a bunch of spike proteins directly, but the evidence is pretty strong that it does.

Here’s a good write-up on mRNA vaccines:

One big advantage I’ve read is that it new vaccines can be developed/produced/modified much more quickly than with conventional methods.

Imagine the virus is a bad guy with a key to your house. Conventional vaccines give your immune system a truckload of mannequins that look just like the bad guy, and your immune system learns to watch out for him. In contrast, mRNA vaccines give your immune system instructions for making copies of the key (the spike protein) to your house, and your immune system learns to watch out for anyone holding a key to your house.

It’s not clear to me what aspect of the coronavirus your immune system learns about when you inject a conventional vaccine (e.g. Johnson & Johnson). If not the spike protein, what is it that the immune system triggers off of?

J&J is not a conventional vaccine. It’s substantially the same technology as the mRNA vaccines in that it codes instructions for your cells to make the thing your immune system is going to react to. The difference is in how that coding is delivered. Pfizer and Moderna use a lipid casing and J&J use a modified chimp adenovirus. The adenovirus technology has been used once before in humans for the Ebola vaccine, but the lipid-based mRNA vaccines have been studied but not approved for use before COVID-19.

The chinese Sinovac vaccine is apparently a inactive-virus vaccine, and it’s apparently not terribly effective.

This is all my best understanding from what I’ve read, but I’m no expert. Happy to have any of this updated or corrected.

A ‘virus’ is a very simple structure: all viral vaccines are ‘substantially the same technology’ – they expose the immune system to something, and you get immunity.

The J&J vaccine and the Sonovac vaccine are both inactive-virus vaccines. The J&J vaccine is an inactive Adenovirus vaccine, and the Sonovac vaccine is an inactive Coronavirus vaccine. Flu vaccines are often made by breaking up the flu virus into fragments. J&J and Sinovac use a different technique to inactivate the base virus.

mRNA vaccines are made by replicating a fragment of a virus, rather than by breaking up a replicated virus, or inactivating a replicated virus.

Another method is to breed a virus that is naturally not capable of replicating in humans, and replicate that, and use it as a vaccine. That takes a very long time, and there have only ever been a few people and a few labs with the time, skill, and dedication to do that.

The Adenovirus used by J&J has been genetically modified (a process similar to egg-sperm genetic sharing), to include a Coronavirus spike. It’s a cross-breed virus. An inactivated cross-breed virus. I don’t think that makes it more similar to a mRNA vaccine, or even to a conventional fragmentation-inactivated vaccine, than to the Sinovac vaccine?

A conventional inactivated virus vaccine (like Sinovac) consists of inactivated target virus, with protein antigens already present. The Sinovac vaccine consists of dead coronavirus virion particles covered in Spike protein. So the protein antigen that we want the immune system to react to is injected “pre-made”.

Whereas the adenovirus vector vaccines (J&J, Astrazeneca) are conceptually much more similar to the mRNA vaccines. In these cases, you are not injecting “pre-made” Spike protein directly, you are injecting the gene that codes for Spike, and instructing the human cells to make the Spike protein. In functional terms, it’s not really correct to think of the adenovirus vector as a “cross-breed” with coronavirus. Adenovirus is a DNA virus. The substantially modified adenovirus DNA vector is a proven tool that is highly effective to place any DNA sequence inside a cell and get that gene expressed by the cell. In this case we place the Spike gene in the vector. The adenovirus vector is not completely inactivated. We need all the adenovirus components that mediate cell entry and that subsequently promote transcription of the DNA to make mRNA inside the cell, so they are all present and functional; but key genes involved in adenovirus replication are deleted.

So the mRNA vaccines and the adenovirus vaccines work in very similar ways in that they both insert the gene for Spike into the host cell, and instruct the cell to make Spike protein. The difference is that the adenovirus vaccines insert the Spike gene as DNA, which is transcribed to mRNA and then translated into protein within the cell; wherease the mRNA vaccines insert the gene in mRNA form.

There’s a good review of adenovirus vectors here - a few years old but it lays out how they work and some of the applications pretty well.

I find it interesting that the 4 most popular vaccines in the English-speaking world all have much more significant side effects in a large percentage of people than most of our older vaccines do. Is there something about the use of mRNA and/or adenovirus vectors that cause the common side effects, or is it just coincidental?

There are currently mRNA flu shots in development and a much needed lyme disease human vaccine candidate is in stage 2 clinical trials right now: if they’re successful, I’m curious if we should anticipate them quite possibly causing you to feel like crap the day after too (and also if they’ll be as effective as the covid vaccines, of course).

I mean, even if the lyme disease vaccine would give you a sleepy/flu-like day, I’d still eagerly sign up; I had lyme in 2011 and it was a pretty terrible 3 weeks, not 24 hours.

Is this true? Is there data that supports this claim? I know side effects have been reported for any large scale vaccination but I haven’t seen anything yet to indicate the COVID vaccines are out of line with past efforts.