[torgoguys]

I don't know much about this, but wouldn't the description of this imply you're stimulating the body to be in an a long-term situation that would be commonly viewed as unpleasant (inflamed, maybe nasal drainage, that type of thing) with the positive tradeoff that you get fewer actual infections?

[MathMonkeyMan]

Yep! But you are also a mouse who has limited venues in which to complain.

I wonder if the vaccine causes inflammatory and other unpleasant responses when administered. If so, I wonder if those responses go away after the last dose, when the three months of protection begin.

Here are the two paragraphs that I found interesting:

> The new vaccine, for now known as GLA-3M-052-LS+OVA, mimics the T cell signals that directly stimulate innate immune cells in the lungs. It also contains a harmless antigen, an egg protein called ovalbumin or OVA, which recruits T cells into the lungs to maintain the innate response for weeks to months.

> In the study, mice were given a drop of the vaccine in their noses. Some recieved multiple doses, given a week apart. Each mouse was then exposed to one type of respiratory virus. With three doses of the vaccine, mice were protected against SARS-CoV-2 and other coronaviruses for at least three months.

[Terr_]

> It also contains a harmless antigen, an egg protein called ovalbumin or OVA

Here's hoping the final product doesn't have a side-effect of inducing an allergy to the main component of egg-whites.

Although even if that happened... Would it only apply to the raw materials, as opposed to cooked products where the ovalbumin was denatured by heat?

Edit: No, wait! What about "safe to eat" cookie-dough, which uses heat-treated flour and pasteurized eggs as ingredients!? The might still have intact ovalbumin, and obviously I can't give it up.

[shiroiuma]

And what about people who eat actual raw egg? I routinely eat freshly-made cake batter (made with raw eggs; I just clean the bowl, I don't actually gobble tons of raw cake batter), for instance. It's perfectly safe because I live in a country where they actually check eggs for salmonella before selling them and people routinely eat raw eggs on top of things.

[kuerbel]

Raw flour is just as dangerous. It can contain e coli and salmonella, among other bacteria.

[riffraff]

AFAIK people with egg white allergy also have to avoid cooked foods.

My understanding (not a chemist nor doctor) is that it's specific bits of the protein that trigger the allergic reaction, so eve if the whole protein breaks down parts of it will survive and will cause trouble.

I suppose this is similar to how we use broken down bits of virus to trigger immune reactions with vaccines.

[Animats]

Right, that's been mentioned elsewhere.

A new area of research has opened up. This approach may be more useful for treatment than prevention. It's not really a vaccine; it's more like an induced vaccine response. Keeping the immune system in that state full time might be a problem. But after an infection, that's what's wanted.

[ipaddr]

Some autoimmune diseases are a result of an immune system always on.

[rossdavidh]

I think that "vaccine" is really not the right word to use for this; they sound as different as bandages and blood transfusions. But if it works as advertised, it could be useful if used in the right situation.

I do wonder if the kind of people who got vaccinated 10 times against Covid-19 will end up trying to get a sniff of this every month? Kind of like how we overuse antibiotics in cleaners. It seems like it would be best if saved for an "oh shoot" kind of situation.

[xattt]

Inoculation?

[rzzzt]

Me neither, but I got something similar from the abstract that I was about to ask, so adding it here: "Following infection, vaccinated mice mounted rapid pathogen-specific T cell and antibody responses and formed ectopic lymphoid structures in the lung."

That latter term (ectopic lymphoid structure) comes up in connection with persistent inflammation where the immune system sets up camp near the problem point. Is this good or bad? Do these go away once the infection clears up?

[dillydogg]

These are pretty common, physiologic structures associated with infections. They can be just a handful of cells on a slide or be quite large, and I don't know what they found in these infections. I didn't read the original paper. The ectopic lymphoid structures go away after the infection resolves. It seems that the immune system has ways to set up mini lymph node architecture right by the site of infections, which is very sensible. The same process is going on in a more organized way in the draining lymph node in parallel. Research into these was really hot in the 2010s, but people don't seem to be as into them anymore (but my research has also transitioned to innate immunity from adaptive, so it's likely that I'm no longer in that universe).

In general, it doesn't surprise me that when you prime the innate immune system, the adaptive immune system works well. The problem is that pathogens have an incredible suite of tools ready to evade these mechanisms. The doses of the pathogens are typically insanely high too, which I do not think model natural infections well. Anyways, this is intriguing, so I'll take a look at the original paper one of these days. Vaccine research generally is so boring. It's like, we vaccinated, and it worked, or didn't, no mechanism.

[modeless]

The tradeoff might not be something unpleasant. For example, it might be that the immune system uses a lot more energy in this state, which would be bad for survival in the wild with limited resources but probably harmless or even beneficial for modern humans with abundant food.

[infinitewars]

Yes, I've had exactly this ever since my first COVID experience. If I come across anyone with even a tiny level of COVID or flu, it sets of inflammation in my lungs within minutes. Haven't gotten sick in six years now but this inflammation has happened probably one hundred times and is indeed quite unpleasant.

[ivan_gammel]

Or worse. If it is so easy to activate, there must be an evolutionary reason why we don’t have it.

[gcanyon]

I think you have evolution backwards. There only needs to not be a reason we need it to survive long enough to reproduce. Or more probabilistically, there needs to not be a significant reproductive benefit to it.

And bear in mind that most people don't have a problem surviving colds and the like long enough to reproduce even with no vaccines at all, and that was probably more true for much of our evolutionary history when we were living much more isolated lives, and not cohabiting with chickens and pigs.

[washadjeffmad]

At scale, yes. Because human males have significantly longer fertility periods than females, the specific adaptations of men who are healthier into later life can be passed onto offspring. The same applies to women who reach menopause while they're still healthy are able to continue caring for family without the risk of expanding the population, albeit for their offspring.

While human evolution is not predictive, it has selected for a wide variety of survival-associated adaptations beyond the mere individual.

[ivan_gammel]

>There only needs to not be a reason we need it to survive long enough to reproduce.

Humans had life expectancy even shorter than our fertility period until recently and they developed as social species hundreds of thousands years ago, for which living beyond fertility period is beneficial (grandparents were invented by evolution too).

> And bear in mind that most people don't have a problem surviving colds

That’s modern people with access to antibiotics etc.

> that was probably more true for much of our evolutionary history when we were living much more isolated lives, and not cohabiting with chickens and pigs

For much of our evolutionary history people were eating animals, getting viruses with them.

[rkangel]

> That’s modern people with access to antibiotics etc.

Antibiotics don't help against viruses like colds. And we live a life that is has a higher degree of social connectivity than our ancestors, allowing for faster spreading of disease, so we're arguably worse off.

[ivan_gammel]

>Antibiotics don't help against viruses like colds

Yes. But they help fighting secondary infections, which are common.

[gcanyon]

> Humans had life expectancy even shorter than our fertility period

That's largely due to infant/child mortality. Once you reached reproductive age, life expectancy was roughly 50, plenty of time to have plenty of kids.

[ipaddr]

If you made it to fertility age your life expectancy was much longer.

[ivan_gammel]

Yes, and to get there we use immunity that is activated on demand. Clearly that was better from evolutionary perspective than preactivation or always-on.

[jmye]

> Yes, and to get there we use immunity that is activated on demand. Clearly that was better from evolutionary perspective than preactivation or always-on.

I don't think you understand evolution. Neither needs to be "better" for anything other than survival to reproduction. Evolution isn't min-maxing in a video game.

[ajuc]

Might be as simple as cost/effect in resource-constrained environment.

Inflamation uses up resources. When we were hunter-gatherers and had to survive ice ages - it wasn't a good idea to waste calories and vitamins just in case.

Better for 3 people out of 30 to die of flu than for all 30 to starve.

Nowadays the optimal trade-off might be completely different.

[tshaddox]

There doesn’t need to be an evolutionary reason why we don’t have something. That’s the default!

[ivan_gammel]

If something clearly helps survival and not an improbable thing to develop, the chances are high we would already have it. But we don’t and most species don’t. It is not the default, there likely exists a reason why.

[tshaddox]

> If something clearly helps survival and not an improbable thing to develop, the chances are high we would already have it.

Well sure, but "not an improbable thing to develop" is doing a lot of work there. Again, everything complex is "improbable to develop," in the sense that evolution takes a lot of time and is very path dependent.

[Larrikin]

What's the reason

[MarkusQ]

Systemic cost.

We could have paper shredders, blenders, toasters, water taps, and so on that just ran all the time, but our utility bills would be ginormous. Same thing for our bodies.

[lokar]

Or the risk of autoimmune disease?

[MarkusQ]

Yep. And probably increased allergies. Possibly decreased fertility. And who knows what else.

[ekianjo]

Yes that's the obvious one

[Rexxar]

Maybe it would made the immune system age faster if it is "used" too much.

[ekianjo]

Inflammation is certainly not "free". It causes systemic damage.

[tensor]

So does getting infected over and over. Much worse damage. Evolution isn't some magic thing that gives you the most optimal creature for a given metric. The only metric is procreation. Not longevity. Not a pleasant life.

[shiroiuma]

>wouldn't the description of this imply you're stimulating the body to be in an a long-term situation that would be commonly viewed as unpleasant (inflamed, maybe nasal drainage, that type of thing) with the positive tradeoff that you get fewer actual infections?

It might be worth it, at least during certain times of the year. For much of the winter, for instance, I already seem to have a lot of nasal drainage and other unpleasant symptoms for the whole time, along with the occasional actual infection which is much more unpleasant.

There's certain times when there's big flare-ups of infections such as flu, so maybe giving everyone an annoying vaccine during that time which gives them the sniffles would actually improve things overall.

[standardUser]

People with severe allergies or at high risk would probably make the tradeoff even if side effects were a problem. If they're not a problem, I could see most people taking this regularly just to avoid the nuisance of respiratory infections.