Single vaccine could protect against all coughs, colds and flus | Hacker News Reader

Single vaccine could protect against all coughs, colds and flus

bbc.com

193 pointsdabinat128 comments

> It is given as a nasal spray and leaves white blood cells in our lungs – called macrophages – on "amber alert" and ready to jump into action no matter what infection tries to get in.

Right and if that is such a good thing why are those macrophages not always on alert. I smell longterm cancer or similar.

> I smell longterm cancer or similar.

Or simply autoimmune reactions which can be devastating.

Yeah this is more likely than cancer, and is a potential side effect of anything that stimulates the immune system, including real antigen-carrying vaccines.

I'm less certain, many if not most lung cancers seems to follow chronic inflammation in the lungs.

The classic example is asbestos related mesothelioma. "Frustrated phagocytosis" is the name for the way macrophages become locked in a never ending spiral of eat, die poison loops around the asbestos.

Do we really want macrophages to go into high gear? Will we make sure no one who has it has been exposed every to any asbestos?

What about other triggers of frustrated phagocytosis? People who commute by subway (tiny metal particles).

The point isn't to say that this is a bad idea necessarily but that I'm not sure this sounds so much safer than regular vaccination.

Indeed, I wonder whether the vaccine content matters at all in current vaccines. We could probably just inject people with the adjuvants and get the same result.

> I wonder whether the vaccine content matters at all in current vaccines.

The target does matter, that is the basis for the whole technology, and the thing most predictive of efficacy. That's why the flu shots often don't work and the shots for smallpox and measles do, the flu is a more rapidly mutating target.

Going crazy with the adjuvants was popular during the pandemic when it became clear that the virus had mutated (the target protein), but no one wanted to do R&D for a new target. Counting white blood cells became a proxy for efficacy, and you can manipulate that stat with adjuvants.

There seem to be cases where the target really doesn’t matter, for example:

https://www.science.org/content/blog-post/mrna-vaccines-and-...

The content clearly matters, and efficacy is tracked (this year it was poor because the eventual pandemic flu strain was a H3N2 virus which mutate rapidly)[0]. This was despite WHO updating the recommendations at the last hour in April/May 2025.

But critically this isn't as important as people think. The primary goal of the flu vaccination is of course to temper spread of the main viruses that season. But it's also to build people's immune library of exposure to flu viruses.

Recall that the 1918 "Spanish" flu was so terrible not because it was intrinsically a worse virus but that it was one which many younger generations had not been previously exposed.

COVID has meant that many younger generations again has a much smaller library of past exposure.

[0] https://www.cidrap.umn.edu/influenza-vaccines/estimated-effe...

Why not just eat a handful of dirt?

This reminds me of an episode in Star Trek: TNG's 2nd season, where Pulaski and Data visit a colony doing genetic engineering experiments on kids which created a super-virus.

It would be nice to have a dosage that lasts a couple of days for when you're flying or attending a conference.

That way, your immune system wouldn't be on continuous high alert, but you could give it an "Oy, wake up. Incoming pathogens." blast.

This. I don't think humans have evolved a brain - immune system pathway to prime the macrophage pump after you book a Ryanair.

If only Stanford University had asked you first!

If only you had read the article.

>There may also be consequences to dialling up the immune system beyond its normal state – raising questions of immune disorders.

> Jonathan Ball, professor of molecular virology at the Liverpool School of Tropical Medicine, said the work was undeniably "exciting" but cautioned "we have to ensure that keeping the body on 'high alert' doesn't lead to friendly fire, where a hyper-ready immune system accidentally triggers unwelcome side effects".

> The research team in the US does not think the immune system should be permanently dialled up and think such a vaccine should be used to compliment rather than replace current vaccines.

They are behind a paywall for Americans now.

Autoimmune disorders

The most likely, because it consumes energy and respiratory diseases take almost nobody from the gene pool.

What has no relation at all to what possible side effects this could have.

there are many, many things our bodies could do (or not do) to greatly improve our health at no cost whatsoever.

That we think have no cost. The massive failure rate of drug trials and some famous cases of issues discovered only after wide scale deployment indicates we're not that great at knowing ahead of time.

The body is like legacy spaghetti code written by hundreds of teams of outsourced engineers. It mostly works. Just never remove any commented out lines or it may break.

Our body was vibe coded

A billion years of kludges.

While possible, there are also many bodily processes that are finely tuned through eons of evolution, and destabilizing pressure leads to disorder. Sometimes it's difficult to know which are which (or at least I don't know).

Which things?

the most straightforward example off the top of my head would be that hair follicles have no conceivable reason to react to testosterone. removing DHT receptors from them would have no adverse effect whatsoever.

have you read the story of dr. adrian thompson's ai generated fpga ? the story goes that removing seemingly redundant components caused the circuit to fail because of second order effects. for that reason, i try to avoid sweeping statements like 'no effect whatsoever' when it comes to playing god

It's important to note that evolution is not a designer, it's just a string of random mutations over millions of years that mostly work. The human body is remarkably shit at a lot of thing, like not getting heart disease. Most animals don't develop heart disease but we do... oops.

We can also live just fine without an appendix. Literally the only thing the organ can do is suddenly develop a severe infection and kill you without surgery which has only become reliably available in the past 100 years or so. (Blah blah bacterial reservoir or whatever: that's of evidently very low value compared to sudden and painful death)

There's also no reason we shouldn't be immune to funnel web poison: cats make an enzyme which deactivates it, whereas primates don't.

There is also no reason our eyes can’t see in the dark because cats can and no reason to not to lay eggs because that’s more practical and way less dangerous (and probably painful) than giving birth directly. Also too bad that we haven’t multiple hearts for redundancy.

Ok.

So what does that means ?

Means there's room for improvement.

That would affect sexual selection, which can have consequences for the following generations, if there will be any.

Or antimicrobial resistance.

My favorite twitter account was “in mice” which just posted stories like this and added “in mice”. Which applies here.

It may come as a shock, but mice are some of the closest species to Humans genetically speaking [0] with 95-99% similarity depending on the gene in question, and a large portion of diseases are shared by both mice and humans [1].

One of the geneticists who worked on identifying this is also on HN and tried to explain this [2] but HNers think they are smarter than actual leaders in the fields of genomics.

[0] - https://www.mpg.de/10973923/why-do-scientists-investigate-mi...

[1] - https://www.mpg.de/8949327/structural-variants-crispr-cas

[2] - https://news.ycombinator.com/item?id=41260651

A top-10 list indicates 6 primates, cat, dog, and cow. While there has been a lot of testing done on primates and dogs, they are much more sympathetic for animal-rights groups, and the general public, when protesting vivisection, breeding, and confinement.

Anatomically and behaviorally, primates would still be the top choices there. And many, many disciplines experiment on animals, where results don't come at the genetic level.

Good, the genetics match closely. But mice (or rats: see the idiom "lab rat") are also considered vermin, prolific breeders, fit in your hand, short life-cycle, and easily obtained. So they join fruit flies in the lab experiments.

Interestingly, pigs are used in many types of medicine while not enjoying that genetic similarity. In the 1950s and 60s, your insulin and thyroid meds were often derived from pigs.

All that may well be true. But one doesn’t have to be a leader in the field of genomics to have read decades of articles breathlessly proclaiming medical breakthroughs (in mice) and then not ever seeing them hit the market (in humans.)

Or in other words the meat of the critique is not aimed at genomics, but rather in science marketing.

You can say the same thing about Phase 1 to 3 as well.

The reality is every theraputic has some kind of negative side effect, which may reduce the incentive for it to be productionized becuase the whole point about medicine is harm reduction.

Passing the hurdle of being viable in mice is a major hurdle because in most cases, experiments fail. And if it's efficacy is proven in mice, it shows viability in a specific approach and justifies investing the hundreds of millions of dollars in trying to bring something to Phase 3.

That's the point though - why does it take hundreds of millions of dollars for phase 3?

Because it happens in a regime that intentionally makes it so.

That's not how e.g. vaccination got invented now is it.

Busy-bodies too busy "protecting us from ourselves" to let us find cures.

I'm not sure why the snark is necessary. Nobody is suggesting that mice are a terrible animal model or trying to tell researchers how to do their jobs, they're just frustrated by pop science coverage that leaves crucial information out of the headline and over-hypes early research. At least the BBC article doesn't bury the lede.

I don't think the problem is specifically mice, but disease models. Some of the hardest diseases to study mice don't naturally (or commonly) get so it has to be induced in some way.

Yes, for example, ALS. Mice don't naturally get ALS and while a somewhat similar condition can be provoked in them, the model does not fit well and seems to be almost useless for producing actual human treatments of ALS.

So you could have kids with a mouse then if you got drunk enough and were un-endowed enough?

Because you typed a number that looks close to 100%. So must be basically the same.

Actually, I think a more to-the-point addition for any headline of the form “X could do Y” is “, but probably not”.

It’s a relative of Betteridge’s Law of Headlines.

I would be interested to see such thing on my Twitter/X feed, is it @_in_mice? It seems to be a bit stale. Would you like to share? Thanks!

We shouldn't call it a vaccine when, in fact, it's just a line of cocaine for macrophages.

PhageRage(tm)

We also shouldn't call it "vegan leather" when it is in fact just plastic.

Naming departs from technical accuracy when adopted by the masses, as they retrofit their common understanding. Wouldn't be too surprised if "vaccine" ends up covering other strong defense-boosters.

> "vegan leather" when it is in fact just plastic.

https://knowingfabric.com/mushroom-leather-mycelium-sustaina...

is pretty neat

Mycelium is neat, but last time I heard of it the problem was far, far too low manufacturing throughput.

I don't think anyone would even consider marketing that as "vegan leather", as doing so would mean putting you in the same bucket as cheap-as-dirt polyurethane (which is what regular "vegan leather" is), at an astronomically higher price. You'd pick a new term to differentiate.

I vote for "shroomskin".

excellent name!

Interesting topic, offensive website. Back to the story …

I found it funny because the opposite direction, people accused Tesla of naming “autopilot” misleadingly, because it gave them the impression of fully unattended self-driving.

In aviation, autopilot features were until recently (and still for GA pilots) essentially just cruise control: maintain this speed and heading, maintain this climb rate and heading, maintain this bank angle, etc.

Because Tesla was claiming in 2016 that "next year" it would be able to drive across the Unted Sttes without any inputs.

Well, okay, but that’s like 95% of flying.

It’s the other 5% that takes 90% of effort :)

Though by the 0.1% highly qualified and extensively trained, so that the chances of misunderstanding by a pilot is like 0.00001% or less.

https://en.wikipedia.org/wiki/Corinthian_leather

Yes, but in this case the name is likely to actually reduce the adoption not increase it.

Wouldn't be too surprised, either - but I still think there's merit in using words in a more precise manner than the marketing department would like to do.

Mushroom leather says hello

A good example for the discussion: leather being animal skin which obviously cannot come from a mushroom.

Assuming you were countering my vegan leather claim: Products marketed "vegan leather" is polyurethane or similar, and for marketing reasons you would use a different term if you did something fancier to differentiate. My gut feeling is that a mycelium-based product would be far more expenisive than simple polyurethane, and quite an upsell.

I mean the word “vaccine” literally specifically references cow pox, so it’s already broadened. No reason not to go up another level.

this isnt exactly a vaccine its more like prophylactic immunoinduction.

"toll like receptors"

https://pmc.ncbi.nlm.nih.gov/articles/PMC7173040/

https://www.sciencedirect.com/science/article/pii/S135964462...

https://link.springer.com/article/10.1186/s40364-022-00436-7

https://en.wikipedia.org/wiki/Toll-like_receptor

Isn't this how "I Am Legend" started?

I wonder how long before this gets defunded too?

Despite a lot of education, I don’t know the immune system well, because it’s complex.

However, it’s my understanding that when the body is in a state of readiness due to its infection (from a cold, flu, etc.) the effects of this (such as fever, inflammation, and general immune response) could potentially could guard the body against other types of infections that the body perhaps doesn’t have resistance to. So while I think a universal vaccine sounds great, I’d try it, and I’d want others I know that have dust allergies, etc. to try it, and because we’ve had friends and family die from the flu, I’m still a little suspicious that this could open the door for other types of disease we’ve not been having to deal with.

This sounds like a great way to create an autoimmune disease.

That's a good chunk of immunotherapy, still super useful.

I'll be fascinated to see how this plays out for people with autoimmune conditions - generalised heightening of the immune system feels like it would be dangerous for those people. Are any immunologists lurking who might be able to speculate?

Its often completely normal to use healthy controls in a trial like this, healthy people not getting ill is your target audience and the long term stage 3 will be against healthy people. So many drugs are not tested against obvious groups that might produce a poor result to make the findings as strong as possible but it means in a lot of cases chronically ill people are making judgements on no data at all.

It seems like it could also be quite dangerous for those with food allergies.

But then it is mentioned that the treatment "also seemed to reduce the response to house dust mite allergens".

The treatment also supposedly activates macrophages in the lungs (and thus not elsewhere). Only some small particles and vapor droplets from foods go into the lungs.

Nice to hear but I'm afraid this will end up like generic solutions, good but not fully effective for single diseases.

Even if it worked perfectly, I would be worried that an unexercised immune system would turn on me.

Macrophages are trash eaters. Keeping them active might even be beneficial for other reasons.

why do they call it a vaccine, its nothing like that...

there's probably a reason evolution didnt put the immune system on permanent "amber alert" as they call it in the article

https://en.wikipedia.org/wiki/Amber_alert

Amber alert means something different than the author thinks ...

They wanted "red alert".

https://en.wikipedia.org/wiki/Red_Alert

This is just an idiom for denoting a high alert state.

No, "Red Alert" is called when there is an attack imminent, incoming weapons detected, enemies sighted.

So a macrophage on "red alert" would be reacting to an active infection or disease.

Sure, and this vaccine goads the macrophage into that state, putting it on "red alert", without there actually being an infection.

I suppose it is not worth debating a metaphor written by BBC reporters for the general public, without even reading the research.

But I was edified to learn that Dr Edward Jenner was a vaccine pioneer even without the honors of knighthood.

Notice that that Wikipedia page links to a disambiguation page which links to https://en.wikipedia.org/wiki/BIKINI_state which may be more familiar to people in the UK than the meaning you are thinking of

Perhaps "Defcon 02" would be better understood?

> The research team in the US does not think the immune system should be permanently dialled up and think such a vaccine should be used to compliment rather than replace current vaccines

True though there is the theory that it was unnecessary for the immune system to regulate itself in some ways because we were full of parasites.

Isn’t Amber alert a missing child? Wouldn’t you say like DEFCON three or something?

This article is from the UK, so it's more like: evacuate the children, Keep Calm and Carry On, but fight them on the beaches.

>The effect lasted for around three months in animal experiments.

It would just be temporary, but there is likely trade offs.

One of the things I do worry about is glasses. Is there a reason why we correct vision? There's probably a reason evolution made some of us see the world in a blur. Likewise with therapy - maybe killing yourself is like cell apoptosis. Many body cells are supposed to choose to die when they no longer function well. It's a good thing. That's often the problem with scientists: "They were so preoccupied with whether they could, they didn't stop to think if they should".

Until we find out why nature made it so some of us kill ourselves maybe we shouldn't fuck with it? Remember Chesterton's Fence.

You're making the mistake of thinking of "nature" and "evolution" as intelligent, reasoning systems, and that every evolutionary adaptation exists for a purpose. Evolution doesn't do things for "reasons," things just happen.

Remember that cephalopod brains are donut shaped and their digestive tracts go right through the middle and if they eat something too big they'll have an anyeurism. Pandas and koalas evolved special diets that serve no evolutionary purpose and both would be extinct if humans didn't find them cute. Sloths have to climb down from trees to take a shit. Female hyenas give birth through a pseudopenis that often ruptures and kils them. Horses can't vomit and if they swallow something toxic, their stomach ruptures. Also their hooves and ankles are extremely weak and not well designed to support their weight. Numerous species like the fiddler crab and peacock have evolved sexual displays that are actively harmful to their survival.

And as for humans, our spines are not well adapted for walking upright, our retinas are wired backwards, and we still have a useless appendix and wisdom teeth. The recurrent laryngeal nerve has an unnecessarily long and complex route branching off the vagus and travelling around the aorta before running back up to the larynx.

Evolution is not smart. Evolution isn't even stupid. It isn't trying to keep you alive and it isn't even capable of caring if you die. Yes we should absolutely fuck with it, because we don't want to live in a world where we still die of sepsis and parasites and plagues because "we don't want to mess with evolution."

>we still have a useless appendix

This was believed in the 20th century, but we now believe the appendix is actually useful, and is basically a fail-safe in case the intestinal flora are wiped out; some will survive in the appendix and repopulate the intestine.

https://en.wikipedia.org/wiki/Appendix_(anatomy)#Functions

Which is an incredibly specious conclusion because when would the gut fauna ever be wiped out? For the evolutionary history of mankind, antibiotics did not exist, and people without an appendix (such as myself) have no medical need for any special treatment after going on antibiotics.

>Which is an incredibly specious conclusion because when would the gut fauna ever be wiped out?

It's called "gastrointestinal illness". From the article I linked:

"Research in 2012 reported that individuals without an appendix were twice as likely to have a recurrence of Clostridioides difficile colitis. The appendix, therefore, may act as a reservoir for beneficial bacteria. This reservoir could repopulate the gut flora following a bout of gastrointestinal illness."

> intestinal flora

> gut fauna

May I be excused? My macrophages are full of slime molds!

Yes, there’s a misconception that evolution leads to optimization and efficiency. It really just leads to traits that are “good enough”.

Evolution has lead to optimization and efficiency many times. It rarely trends to maximization or the largest possible efficiency, since those conflict with "good enough". Protein structure and function is a common example.

> It rarely trends to maximization or the largest possible efficiency, since those conflict with "good enough".

Sometimes things get trapped in a local minima. Particularly when a seemingly inconsequential detail at a much much earlier stage becomes a dependency of lots of downstream stuff, but then it turns out that this just so happens to conflict with a better option in the here and now.

More commonly, the "perfect" solution is extremely brittle while the (supposedly) "good enough" solution is incredibly robust to all sorts of environmentally inflicted bullshit. In other words, most of the time evolution is practical while the humans criticizing the outcome are ignorant idealists.

I would go so far as to say that the vast majority of the time, systems that evolved are robust, not brittle, and you're right, this compromise "works better" or is "good enough to reproduce more than my relatives". And other times something gets caught in a local minima- but other bits around it optimize anyway (I think the "backwards" human eye might be an example of that- https://en.wikipedia.org/wiki/Evolution_of_the_eye#Placement and see also, https://en.wikipedia.org/wiki/Evolutionary_baggage).

Anyway, the example I was thinking of is here: https://en.wikipedia.org/wiki/Diffusion-limited_enzyme where some enzymes have evolved to reach extremely close to the maximum rate of catalysis limited by diffusion rates (and some enzymes have clever tricks to get around that).

Not even good enough: "population reproduced faster then it died".

That's it: and it's separate from good enough because that can include things like "happened to live on the part of the island which didn't get obliterated by a volcanic eruption at the only point in history that volcano ever erupted".

>koalas evolved special diets that serve no evolutionary purpose

Koalas biggest problem is us? Like they seem perfectly adapted to their niche. Eat lots of leaves that nobody else is adapted to use as food, and once a year, run very fast to outpace the bushfire that your principle food source needs to reproduce.

FYI horses are the product of domestication.

Fair enough.

In my defense, domestication is still technically an evolutionary process.

Are their hooves, though? The fossil record clearly shows a progression in their ancestors from having feet with many toes to the single "toe" they have now.

Huh, that's really interesting. But I suppose it doesn't apply to the amber alert thing. In that situation, evolution probably was an intelligent reasoning system that existed for a purpose and we must be subverting it (a bad idea). There's always an exception to every rule, I suppose.

Evolution is never an intelligent reasoning system, any more than gravity ever is.

Never? Not even the OP's «there's probably a reason evolution didn't put the immune system on permanent "amber alert" as they call it in the article»? Oh, that's surprising. Well, TIL.

Some groups of people have evolved to believe that, anyway.

Although we don't have a lot of hard evidence, there is reason to suspect that the high rate of poor vision in modern young people is more environmental than an evolutionary flaw. We spend too much time indoors staring at nearby objects under dim artificial light. People who spend most of their time outdoors are less likely to need vision correction, although there could be trade-offs later in life as the damage caused by natural UV light accumulates.

IIRC, we do have evidence that myopia started to decline (in the population) in Singapore as soon as the city applied strict rules for enforcing outside activities for the children basically every day.

I remember that the effect in the tendency was more or less immediate.

The reason we correct vision is for safety and convenience. My guess is that we have a distribution of vision capabilities due to the inability of complex biological systems to ensure that the precise geometry of the cornea and lens is subject to statistical variations that can't be controlled. There are probably also tradeoffs associated with near and far vision.

Now, you could have restated this in a better way IMHO. I'd put it like this: are there any evolutionary advantages to having worse-than-average near or far vision? For example, we can imagine that people who had extremely good long range vision would be more successful in hunting, and perhaps- this is where I'm speculating heavily- having poor long vision is compensated by having better detail vision for fine tool work. However, what I've learned after many years is that attempting to perceive the true nature of the evolutionary fitness function is challenging.

As for your bit about suicide: please be a lot more thoughtful in speculating about suicide.

I had to upvote this just because it's such an incredible take, it really made my day even if I think it's complete horseradish

C'mon now, it's probably one of the better trolls I've seen today.

Poe's law and all, but the first two responses to this are missing some sarcasm that looks pretty overwrought to me.

Really...?? :)

"Sorry son, you can't get these glasses. It's for the betterment of humanity."

I think you missed their sarcasm

... Yeah probably huh :)

You just don't know sometimes.

This isnt a vaccine against suicide.

Are you wildly speculating or do you have a source with research backing up your claim evolution got it perfectly right?

I personally look forward to every innovation that potentially improves our baseline.

They didn't claim evolution got it perfectly right.

They speculated that immune systems evolved to avoid being continuously on alert. And that's exactly right- our immune systems have an extremely complicated system for detecting foreign invaders that is tightly regulated. And a failure to regulate that is often associated with autoimmune disorders, which remain very poorly understood.

I've studied biology from the perspective of engineering better drugs for decades now and I can say with confidence that I simply don't understand how the immune system works, and I don't think anybody else really does either (compared to, say, the heart, or many biological systems like protein production). We have identified many players, and observed a great deal of actions, and have speculative models for many of the underlying processes, but we don't really have an "understanding" of the immune system. I skimmed this paper and frankly, it has a very long way to go before people are convinced to try this in human clinical trials.

I look forward to innovations, but to a first order approximation: evolution found model parameters that exceed the best human science and engineering.

I bet my money on the immune system any day.

Hard to beat a half million years of evolution with a nasal spray from last year.

You don't have to bet money on it.

You can just stop taking antibiotics and vaccines.

Those are way more interesting odds.

(Most) vaccines work by letting your immune system know to watch out for particular things. That's an information advantage. Likewise, antibiotics are chemical agents that the body lacks the genes to synthesise. Betting that the immune system's parameters are generally well-calibrated is entirely compatible with taking antibiotics and vaccines, where indicated.

You wouldn't want to get vaccinated for smallpox in the middle of a plague epidemic, because that would waste your immune system's resources on an extinct-in-the-wild disease, when it really needs to be gearing up to stop the plague killing you.

The immune system does not expend resources on vaccines.

You do not somehow go into deficit by getting a vaccine.

The immune system does expend resources on vaccines: it makes antibodies, usually has some kind of inflammatory response…. But if a vaccine causes a nutritional deficiency, there's something seriously wrong with your diet.

This is like saying that balancing while walking expends resources.

Yes it's technically true, but it is also how walking functions regardless of circumstance.

is this a new series?

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