Universal vaccine against respiratory infections and allergens
med.stanford.edu
med.stanford.edu
ie what has driven human population growth - a fundamental change in availability of natural resources or a fundamental change in how humans exploited them?
I'd argue it's the latter, and that's driven by accumulated knowledge - and before writing - the key repository of that was - old people.
Part of the reason it benefited us that some but not all people become old is because people require more attention during two phases of their lives. Our biological evolution has prioritized care for the very young over the very old, with respect to a limit on resources (like attention), effectively until the modern age. In some cultures, for instance, those with teeth must pre-chew food for those without, or expected members to engage in ritual suicide at a certain age.
It's like saying cars pistons are designed to wear out - because they do and as the car is perfectly designed ( the mistake ) then it must be for a reason.
Also take menopause - it happens a female has all the oocytes ( eggs ) they will ever have already at birth. Menopause happens when they run out.
What you are arguing is that the number at birth is optimised with a very indirect feedback loop - as oppose to a very direct one of how much resources do you put aside for eggs in terms of maximising number of direct children versus resources used. Occams razor suggests the latter is going to be stronger.
If what you say is true - think about it - old people wouldn't gradually crumble due to wear and tear, they would have evolved some much more efficient death switch. ie Women don't suddenly die post menopause.
How much accumulated knowledge do hunter-gatherers have?
One of the risks of an always on response, is if something evolves to evade it - you have nowhere to go.
It's why taking an antibiotic at breakfast everyday is not a good idea.
Eh, the main downside in the short run is that you are killing your gut fauna.
> One of the risks of an always on response, is if something evolves to evade it - you have nowhere to go.
Evolution can't look into the future. (And eg bats are pretty much always on with their immune system.)
Sure. But yesterdays mistakes can be punished today. ie all evolution happens in retrospect - a mutation haopens - the world tells you after the fact whether that was good or bad. Evolution is hindsight in action. In hindsight - taking antibiotics everyday might have been a bad idea.
> Eh, the main downside in the short run is that you are killing your gut fauna.
Sure - thus increasing your chances for being colonised by an unfriendly and antibiotic resistent bug - which may result in your death - which in hindsight was obviously a bad idea....
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.
The current framework of our immune system could go back quite some time. Even to our mammalian cold-blooded ancestors, 200? mya. When I think of cold blooded, I think of creatures able to remain static and at rest for a long time, periods of low-energy usage. So maybe this framework comes from before warm blooded mammals?
And, if it works well enough that people can breed (which used to be 15 years to 30 years old), and if dying after, oh well. Why evolve better? Or maybe too much monkeying has downsides.
Look at sickle cell anemia. Quite beneficial with malaria parasites around, not so much without them.
So I'd lose weight too? Sign me up yesterday.
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.
Graves’ disease, lupus/SLE, psoriasis, type 1 diabetes, myasthenia gravis, Addison’s disease, Hashimoto, Goodpasture, etc.
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?
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.
Couldn’t you apply this logic to any medicine?
A vaccine or inoculation is named because it creates a sustained adaptation to a targeted antigen. Something that boosts immune response is not an acquired adaptation! This would need to be re-upped every month or so.
Good for travel and brief encounters. Not an actual immunization.
Not too mention boosting cell growth factors can have unintended side effects like cancer! There are immune system cancers and I would be concerned about risks there.
What this treatment does is the opposite side of that coin, it mimics cytokines in order to PROMOTE an immune response.
Immune regulation is an area that deserves a lot more research, and there is going to be learning (harm) along the way. An increasing body of science is pointing to autoimmune diseases being triggered by traditional vaccines, which are then treated by the biologics above that increase the likelihood of other disease due to immunosuppression, which can now be treated(?) by a new immunobooster AKA universal vaccine?
My wife has an autoimmune disease. Most all the evidence points towards gut biome but that shit is super complicated. We have very little research into what our gut biome needs to be.
Great for the investors though? ;)
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?
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.
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.
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.
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.
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.
This doesn't mean anything.
> Chances for survival to reproduce of some individuals are greatly influenced by survival of their relatives in the same group. The traits that help whole group to survive will win in natural selection, including those that extend survival beyond what’s necessary to reproduce to what’s beneficial for the group.
Which, of course, has absolutely nothing to do with whether current traits are optimized for perfection, or simply sufficient for continued reproduction. Again, evolution isn't min-maxing your video game character. I'm not clear why you have such strident opinions on something you don't understand very well.
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.
Yes. But they help fighting secondary infections, which are common.
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.
While human evolution is not predictive, it has selected for a wide variety of survival-associated adaptations beyond the mere individual.
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.
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.
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.
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.
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.
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.
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.
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.
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.
When, specifically, do you think that has happened? I'll wait.
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.
This looks like the inmune system is keep at the emergency level for 3 months.
These two things have literally nothing to do with each other.
> I get sick after getting the flu vaccine and feel pretty bad for 1-3 days
I thought you skipped it every year? So did this happen like, once, and you don't actually have any real basis for comparison or understanding, here? Come on.
Probably n=5 or 6 out of 18.
I don't know why people feel so compelled to invent stories about vaccines they hate but don't even vaguely understand, especially when the creative writing is so poor. It's such a weirdly pervasive thing in healthcare, that people think basic existence is the same as expertise.
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.
The innate response is less targeted, less effective, and causes potentially damaging effects like inflammation. The adaptive response is more targeted and more effective, with the tradeoff that it needs to be learnt.
Meanwhile, if you've got spare millions laying around, have a look at ENA Respiratory. They've already done a Phase 1 in Australia (entirely admissable for the FDA). Turns out hypoxia creates and anxiety and old people have most of the world's wealth, so COPD is a lucrative market.
Another super interesting one is Lumen Biosciences - can't make oil from algae at a viable price point, but for sure they can hit pharma price points, even food supplement price points.
Some discussion: https://news.ycombinator.com/item?id=47080267
At first they helped against a broad spectrum of bacteria but then the bacteria evolved.
Damn you Darwin and your evolution.
It was a pretty life changing surgery that finally allowed me to properly sleep again, and do exercises/run while breathing through the nose. For some people, the turbinates may become enlarged again after a while, but for me it's been great for two years already.
I tried hyposensibilization therapy, and while it worked for seasonal birch pollen issues, it didn't work for dust mites, oral allergies, and chronically stuffed sinuses.