Universal vaccine against respiratory infections and allergens (med.stanford.edu)

I was thinking the same thing. Perhaps the trade-off made by evolution is about saving energy?

In that case it shouldn't be a problem to boost the innate immune system, as long as you have surplus calories to spend. But it could be something else entirely.

Such as autoimmune disorders or other hyperinflammatory disorders?

Graves’ disease, lupus/SLE, psoriasis, type 1 diabetes, myasthenia gravis, Addison’s disease, Hashimoto, Goodpasture, etc.

Evolution just needs people survive long enough to reproduce. If they get sick afterwards, it doesn't care.

You wouldn't have to do it all the time. Modern humans are much more likely to get a respiratory infection in the winter (I get sick once a year like clockwork). It could be worth stimulating your innate immune system for a few months every year during flu season. Or before traveling.

> cranking up the innate immune system all the time reduced illness with no downsides

But isn't that what the adjuants that are currently in nearly every vaccine do anyway. That is forcing the triggering of immune response when there wouldn't be none or very little response naturally?

But evolution is not optimizing for best outcome in terms of health. As Dr Karl said, "Evolution does not have to be perfect, just good enough for you to have babies & get them to maturity".

> you'd think evolution would have done it already, but it didn't, which makes me think there's probably a downside

Couldn’t you apply this logic to any medicine?

It’s only an imperfect vaccine — broad immune protection. Evolution probably has come up with a bunch of these.

Evolution is not a perfect optimizer.

That’s not how evolution works.

> If cranking up the innate immune system all the time reduced illness with no downsides, you'd think evolution would have done it already, but it didn't, which makes me think there's probably a downside,

Auto-immune diseases are the downside. There is no way that this ends up being safe or recommended for use outside of epidemic situations or short term occupational hazards.

It's probably because maintaining the immune system at high levels costs more energy.

You probably know that antibiotic use is rampant in industrial livestock. But do you know precisely why?

Antibiotics aren't just given prophylactically to prevent infections; constant low doses actually *increase the animal's size*. The animals can put more energy into growing larger, and spend less on their immune system.

They’re largely an artifact of civilization, with people living in close proximity to lots of other people, and to livestock. We haven’t had time to evolve for that new reality.

Also the obligatory, “in mice”.

I would also mention, just general auto-immune diseases. I would be very worried this could trigger those in people who wouldn't have gotten one otherwise.

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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.

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.

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.

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?

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.

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

>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.

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.

They say so in the article but you need a teensy bit more to make the connection. Here's the ELI5 version and then a link to too much detail:

You can have a Th1 or a Th2 reaction. One produces one kind of reaction and the other produces a different kind of reaction. And they both inhibit the other. It's a mechanism whose purpose (to the degree purposes exist) is to identify which kind of problem you have and apply as much energy as possible to that because they each fight different kinds of enemies. You'll see in the article they say:

> Allergic reactions are caused by a type of immune response known as Th2 response. Unvaccinated mice showed a strong Th2 response and mucus accumulation in their airways. The vaccine quelled the Th2 response and vaccinated mice maintained clear airways

Neither of these are immune (haha) to causing problems. Th1 was historically associated with multiple sclerosis. Obviously if your detection mechanism is broken you will create more and more of the wrong kind because of the fact one kind can beat the other with numbers but also because the wrong one won't even get the mis-detected enemy (which might not even be an enemy - and be harmless) out.

The too-much-detail: https://pmc.ncbi.nlm.nih.gov/articles/PMC27457/

> Th1-type cytokines tend to produce the proinflammatory responses responsible for killing intracellular parasites and for perpetuating autoimmune responses. Interferon gamma is the main Th1 cytokine. Excessive proinflammatory responses can lead to uncontrolled tissue damage, so there needs to be a mechanism to counteract this. The Th2-type cytokines include interleukins 4, 5, and 13, which are associated with the promotion of IgE and eosinophilic responses in atopy, and also interleukin-10, which has more of an anti-inflammatory response. In excess, Th2 responses will counteract the Th1 mediated microbicidal action. The optimal scenario would therefore seem to be that humans should produce a well balanced Th1 and Th2 response, suited to the immune challenge.

> Many researchers regard allergy as a Th2 weighted imbalance, and recently immunologists have been investigating ways to redirect allergic Th2 responses in favour of Th1 responses to try to reduce the incidence of atopy

There's a lot of detail to it. After all, it's an emergent evolved device that we carry, but that's the rough shape of it. You can create one kind of immune response and simultaneously shut down another kind.

Allergies are not simply overactive immune response. It’s the wrong type of response. What’s really intriguing is how much we can do innate immunity that we have done relatively little with.

I'm pretty allergic most of the time (lots of birch cross allergies and dust mites), but sometimes when I'm sick the allergic reactions appear to go down. Allergies can be pretty weird.

I would speculate it's something like, if your innate immune system is running "hotter", it's going to reduce the amount of time it takes to clear anything it runs into, leading to less time spent inflaming anything, in a similar fashion to how it significantly reduced viral payloads, leading to negligible symptoms when the adaptive immune system batted cleanup.

> [greater activity within] our immune systems long-term can't be healthy

Not trying to be flip, but why? "Natural" isn't always better, and as the obesity epidemic has shown, our evolutionary past hasn't done a perfect job of preparing us for our current environment.

You might be right, but I'm skeptical that there is any non-extreme limit to something as simple and mechanical as our innate immune system.

Cant we say this applies to the flu vaccine? This almost validates why I skip it every year.

I get sick after getting the flu vaccine and feel pretty bad for 1-3 days... then I get the flu anyway because they picked the wrong ones.

It could also be useful in low doses to supplement, for example, a seasonal vaccine in a year where they are especially unsure about prevalent strains, or where their predictions were already proved wrong early in the flu season

you would think so! as a "vaccine skeptic", i think this kind of research is important and patients should be able to decide w/ their doctor which to pursue based on their individual condition. perhaps this tradeoff will be worth it in higher risk individuals.

No need: this is always the top comment

Depending on how bad it is for you, I can recommend thinking about turbinectomy. Had it done due to chronic, allergy related swellings, and it was life changing.

Gotta start somewhere!

Intranasal, no jabs

The only human disease that has been eradicated is smallpox. What did that get relabeled to?

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