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Comment by fabian2k | Hacker News Reader

If there is one thing I certainly wouldn't just play around with it's the immune system. It's incredibly dangerous and easily capable of causing all kinds of harm to yourself up to killing you outright.

A vaccine is designed to produce an immune response of the right magnitude. Too low and it doesn't work, too high and it'll cause damage. At least one of the vaccine candidates in development was put back to the drawing board because the immune response wasn't strong enough. So this is not an area that is entirely predictable, you have to carefully test this to know if it works.

I'd also be very careful about the inhalation route. Inhalable insulin is a well-known failure, in part because of side effects due to the inhalation. And that is a protein that isn't designed to activate your immune system.

I also hope the synthesized peptides were carefully purified, you really don't want to inhale e.g. residual trifluoracetic acid.

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I recall a researcher talking about previous attempts at creating coronavirus vaccines. How they resulted not in immunity, but in training the immune system to _over_ respond when a real infection came along.

After a bit of digging I found this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/

> An early concern for application of a SARS-CoV vaccine was the experience with other coronavirus infections which induced enhanced disease and immunopathology in animals when challenged with infectious virus

I didn't dig deep enough to see if any experimental vaccines caused similar issues, but it definitely appears to be a concern.

So yeah, I'd be _very_ cautious with any homebrew vaccine. You might accidentally train your immune system to self destruct when you get exposed to a real SARS-CoV-2.

That said, I have little to no experience with biology, so it's entirely possible that radvac based vaccinations have already been demonstrated not to have this particular problem.

A recent attempt at a dengue vaccine faced a similar problem. The most dangerous kind of dengue fever happens when you are infected a second time, by a different variant than you were infected the first time. It turns out that the vaccine ended up having a similar effect as catching dengue for the first time. People who never had dengue and got vaccinated had a lower chance of catching the disease in the future. But if they did catch it there was a higher risk of it being the more dangerous version. The end result is that the vaccine is now only recommended for people who already had dengue before.

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

This is specifically mentioned in the Radvac paper in the section titled "POSSIBLE MECHANISMS OF VACCINE-ENHANCED DISEASE, VACCINE-INDUCED AUTOIMMUNITY, AND MITIGATION STRATEGIES"

> train your immune system to self destruct

Might be a nitpick, but the immune system destroying itself would be a different, still possibly dangerous outcome of probably losing your defenses.

An over-sensitized response would be a hyper-sensitive trigger-happy paranoid all-hand-on-deck general-mobilization fight-or-die this-is-the-end immune response, of various scale, possibly similar to but not exactly the same as a bad case of covid.

Homebrew seems unfair: https://radvac.org/a-homepage-section/

Trying it is IMHO a risk calculation once you've jumped the "is this credible" bar.

Super-dumb question: Could you try it out on a rat or a vial of your own blood first?

Not a dumb question at all. In medicine we test on two different animal species before it goes close to a human. For a reason.

The sites where the body evolves adaptive immune responses like antibodies and killer T cells aren't actually in the blood so that wouldn't produce any result. Rats don't have good ACE2 receptors for getting sick with Covid-19 but ferrets do so you could try testing this on them.

Can you provide more information about how vaccines can cause damage?

I said that the immune system can cause damage. Vaccines have a very high safety standard as they are given to large numbers of healthy people, so the tolerance for serious side effects is very low. So the development there is very careful, and anything that looks too dangerous is hopefully caught in animal experiments or at worst at phase I.

A well known example of how dangerous the immune system can be is the following phase I trial:

https://www.nejm.org/doi/full/10.1056/nejmoa063842

That drug caused a cytokine storm in the participants in the phase I trial.

Allergies are another example of how dangerous the immune system can be if it is triggered against the wrong targets.

I have suspected for much of the last year that a lot of people are running on an unexamined "Only crazy people think vaccines cause autism -> Only crazy people think vaccines are ever dangerous in any way -> All vaccines are perfectly safe" psuedo-syllogism.

This is false.

Put another way, the very fact that we run such massive tests on them before deploying them is itself evidence that the wrong ones can be very dangerous. (Mostly, as I understand it, "very dangerous" to a small set of people who will have very large reactions, even if most people are fine. The ones that are very dangerous to everyone never gets past the initial phases at all, of course.) We're not doing that because vaccines are all perfectly safe under all conditions, but we just want to hold them back for a year for no reason. We're doing it because we need to be very careful with them.

Though I'd also observe a non-trivial component of that danger is also because we're injecting them. Bypassing the body's co-evolved with the environment's defenses is not to be done lightly. This sort of inhaled vaccine is likely to be much less dangerous. I won't say "safe", but less dangerous; the body already has to deal with essentially arbitrary small amino acid sequences being inhaled all the time. I'd still be a bit worried about sythesizing things that we haven't co-evolved with.

(If you don't know what co-evolution is, I'd suggesting taking a moment to learn about it: https://www.britannica.com/science/coevolution It's a very important part of understanding the disease landscape holistically.)

It is all about risk/reward.

Covid is very deadly right now, it is the leading cause of death in several countries, including the US. If you catch covid, it roughly doubles your chances of dying for the year, and without a vaccine, it will happen eventually.

It means that even an "unsafe" vaccine, you are better off taking a shot.

On the other hand, a flu shot has to be extremely safe, because the flu is much less deadly, and the flu vaccine seems to be less effective than the covid vaccine. So most vaccines are pretty close to perfectly safe, the covid one, maybe a bit less so, but it is still worth it.

The thing is that we are biased. We will focus on the one person the vaccine has killed, but not the ten others the vaccine has saved. Just like with the trolley problem, will you throw someone under a bus if it can save five people?

> the leading cause of death in several countries, including the US

One good thing about living in this time is that facts are trivial to look up. All the stastistical data is publicly available.

The leading cause of death in the US is still heart disease, then cancer.

> If you catch covid, it roughly doubles your chances of dying for the year

Not according to the CDC statistics, unless you mean some specific group, such as those aged 85+.

How many people even knows what chance it is they will die this year?

https://data.cdc.gov/NCHS/Monthly-Counts-of-Deaths-by-Select...

Right now, covid is the leading cause of death. It wasn't the case in 2020, but now, it is.

For the "roughly doubles", it is, as I said a rough idea in a high income country, something I forgot to mention. It is probably less overall but not by a huge amount. It is relatively consistent with a 1% IFR. It is age dependent but surprisingly not by that much, simply because older people are more likely to die of any cause.

> How many people even knows what chance it is they will die this year?

That question is meaningless. The nature of probabilities is that you don't know. For example, if you are playing Russian roulette, just before you press the trigger, you can estimate your chances of death quite accurately to be 1/6. But there is no intrinsic value to that number. To someone who can see the bullet in front of the hammer, it is closer to 100%, and to someone who knows the gun is jammed, it is closer to 0%.

>Right now, covid is the leading cause of death. It wasn't the case in 2020, but now, it is.

Are you implying you think covid will kill more americans than heart disease in 2021 based on this incomplete data set?

>>How many people even knows what chance it is they will die this year?

>That question is meaningless.

It is not meaningless for people who care to take personal responsibility for their own health, and who want to make informed decisions based on a data driven risk analysis.

However, most Americans do not care to take personal responsibility for their health, so you're right that such people are not concerned with such information.

>Covid is very deadly right now, it is the leading cause of death in several countries, including the US.

This is misinformation.

Heart disease is the leading cause of death in the US, killing around 650,000 americans each year[1]. Also note that heart disease and obesity are extreme risk factors for negative health outcomes from covid, leading to potentially 3x the risk of hospitalization.[2]

Populations suffering from prexisting obesity epidemics, such as America and Europe, have had far worse health outcomes from covid than Asia and Africa, which have no obesity epidemic.[3][4]

>If you catch covid, it roughly doubles your chances of dying for the year

Do you have a source for this? I'm assuming this is not true for young and/or healthy people.

[1]https://www.cdc.gov/heartdisease/facts.htm

[2]https://www.cdc.gov/obesity/data/obesity-and-covid-19.html

[3]https://ncdrisc.org/obesity-prevalence-map.html

[4]https://en.m.wikipedia.org/wiki/Coronavirus_disease_2019#Mor...

The thing with covid is the younger/healthier you are, the less likely you are to die from it, but you are also less likely to die from anything. So the relative risk does not change much.

In Africa, the population is much younger than in the US and life expectancy is lower. People die from other causes like malaria, malnutrition, violence, etc... much more often than in the US, so mechanically, the relative risk of dying from covid is lower.

In rich Asian countries like Japan, I haven't heard of a significant difference in infection fatality rate compared to western countries. They have less deaths overall because they have less cases, certainly because they manage the pandemic better. In poor Asian countries, it is essentially like Africa.

As for obesity, it is actually worse in northern Africa than in Europe, and closer to the US. And southeast Asia is getting close to Europe as these countries develop.

>The thing with covid is the younger/healthier you are, the less likely you are to die from it, but you are also less likely to die from anything. So the relative risk does not change much.

Exactly my point. Covid is a negligible risk to young healthy people compared to elderly, sick, obese people. This will have an effect on their risk calculations determining if they should take a vaccine which was rushed through safety trials or to take on a virus naturally which their immune systems can easily defeat, according to the data.

>In rich Asian countries like Japan, I haven't heard of a significant difference in infection fatality rate compared to western countries.

If you look at the data, you'll see the significant difference.

The US has 139.30 deaths per 100,000 people from covid.

Japan has 4.88 deaths per 100,000.[1]

>As for obesity, it is actually worse in northern Africa than in Europe, and closer to the US. And southeast Asia is getting close to Europe as these countries develop.

Indeed, if you look at the obesity map and the covid map of the world, you'll see the same correlation of obesity and larger relative covid risk in northern Africa.

[1]https://en.m.wikipedia.org/wiki/COVID-19_pandemic_death_rate...

Probably the best example of this is the live oral polio vaccine. It's a bit risky (it occasionally reverts to being infectious) but in a population where polio is endemic it's much safer than letting polio keep circulating.

(In places where polio isn't endemic, you get administered a totally inactivated vaccine by injection instead. They don't give everyone that one because it's more complicated to distribute, the oral one needs much less infrastructure)

Another advantage of the oral vaccine is that it produces better immunity in the gut, which helps cut off assymptomatic transmission in places where polio is still endemic.

End of the day, we evolved and are bred to recognize patterns and project outcomes based in what we see. The problem in modern society is these instincts make us vulnerable to poor risk management.

The relationship between “crazy” antivax people and the actual attributes of a vaccine are not correlated. Antivax is a con game. Bad actors take advantage of natural instincts (ie protect your children), project false qualification and leverage ignorance to push their narrative, and usually product.

[Deleted. I didn't fully read the parents post, and responded emotionally. That was wrong of me and I apologize]

If you think carefully, you may realize that what you said is actually entirely unrelated to what I said.

Perhaps you are not one of the people running on the unexamined assumption. I still say it's clearly operative in many people.

I call it "unexamined" precisely because once pulled up the conscious level, it is obviously false. Nevertheless, pulling such things up to the conscious level is not easy and usually takes effort. Or, to put it another why, while I cringe every time I adopt this terminology, Kahneman's System 1 is pretty sloppy about such things. System 2, when presented with a problem directly, can often see quickly that System 1 is being irrational... but it first must be presented with the problem directly.

Yes you are right. I like to think im better than that, but in this instance i clearly wasn't.

If i can quibble though, i think "all" can be a bit of a loaded word in this context, because people often use it to mean, all well known ones or something along those lines and not all potential ones including random stuff people make in their backyards.

I personally know very intelligent and highly educated people who went to top universities who are convinced vaccines caused mental retardation in their children. They may be wrong, but I would not call them nutjobs.

> "very intelligent and highly educated people who went to top universities"

Imagine trusting a "rocket scientist" to even weigh in on medical topics because they are "very intelligent" in their totally unrelated field. This is an unfortunate misconception that plagues conspiracy theory extremists who reference PhD graduates in their arguments against things like 5G brain control.... pointing to people with doctoral degrees in Music or something.

Look I am not saying they are right. My point is these are not your average stupid uneducated person. The two families in question, the one parent has multiple PhDs from Columbia and Princeton, the other took their undergrad at Caltech. You don't get those degrees by believing any random crazy thing that crosses your path. Plus they have a first hand experience with their child that for some reason makes them believe the vaccine was responsible. If it were any other topic their background and experience would lend their viewpoint more credence than dismissal as "nutjobs". What makes this topic different? Why would they have any incentive to blame the vaccine besides some sort of convincing first hand experience? Why should we in this one instance distrust their rational capacities that have allowed them to acquire intellectual credentials the vast majority of the earth's population don't have the capacity to acquire?

Being smart and being crazy are not mutually exclusive

I think it’s more accurate to say that intelligence is not adequate defense against trusting the wrong sources of information, and people are extremely resistant to changing their minds once they’ve placed a stake in the ground.

I'd go with both. There are plenty of smart people who i would consider delusional. Which is separate from people stuck in their views.

However, as the saying goes, science advances one funeral at a time.

“According to the CDC, in the United States as of January 19 there were 45 cases of anaphylaxsis with the Pfizer shot out of the several million given.” https://www.wtkr.com/news/gloucester-resident-dies-within-ho...

The UK regulator published the first set of data from the rollout of both the Pfizer and AZ vaccines today: https://www.gov.uk/government/publications/coronavirus-covid...

> The MHRA has received 101 UK spontaneous adverse reactions associated with anaphylaxis or anaphylactoid reactions with the Pfizer/BioNTech vaccination. All patients have recovered from the anaphylaxis episode. 13 reports of anaphylaxis have been received for the COVID-19 Oxford University/AstraZeneca vaccine to date.

> As of 24 January, an estimated 5.4 million first doses of the Pfizer/BioNTech vaccine and 1.5 million doses of the Oxford University/AstraZeneca vaccine had been administered, and around 0.5 million second doses, mostly the Pfizer/BioNTech vaccine, had been administered.

Yup, and this is a few times worse than we're used to with widely used vaccines.

For a rare disease, this would be pushing the rate of side effects and risk that is acceptable. But you've got a huge risk of catching COVID, and COVID is many orders of magnitude more dangerous than the vaccine. At least for now: if COVID vaccination is required in the long term, vaccines may have to get better.

An issue here is that no one could risk the vaccine failing, with the limited time we had and the massive trial. In a normal process, it's likely that smaller doses would have been selected. But here it looks like both Pfizer and Moderna "rounded up" a bit from what phase 2 trials pointed to as doses. If I were in charge, I'd have funded a non-inferiority trial in December for 1/3rd dose, which would put us in a position in February-March to massively stretch supplies and reduce side effects.

Thankfully that's a rare side effect and one that the nurses giving the injection can recognize and deal with. No fun for the recipient but nobody has died or suffered lasting injury. This is, however, why we don't conscript people to give vaccine injections.

Only crazy people think vaccines cause autism. Nobody thinks vaccines are 100% safe. That’s a red herring.

Vaccines that go through proper testing have a very high bar for safety but nothing is 100%.

> Only crazy people think vaccines cause autism.

This is simply not true. I've talked to a psychologist who treated kids with autism about this. Autism is usually diagnosed at a young age when children develop and also get vaccinated. This leads to bias in some of their parents who are looking for someone or something to blame for their misfortune. Combine this with the fact that in the last two decades diagnostic for autism was extended to other less severe disorders such as Asperger's. If adults would develop autism after getting vaccinated, then it would support this crackpot theory, but they don't.

Crazy is perhaps not the most accurate word but you get the point.

I have no doubts about the safety of vaccines in healthy people. I have some harmless curiosity about people who are not known to be healthy. How do you actually determine if someone is "too immunocompromised" for a vaccine?

This must be a question with no good answer.

> I have no doubts about the safety of vaccines in healthy people. I have some harmless curiosity about people who are not known to be healthy. How do you actually determine if someone is "too immunocompromised" for a vaccine?

My understanding is that being too immunocompromised for a vaccine happens in two different ways:

1) the vaccine contains live virus and so there's danger that the weak immune system couldn't fight this off

2) the vaccine isn't live, so it's not dangerous on its own, but the immune system is too weak to recognize it, so it doesn't build any immunity to the real thing. (One doctor I was talking to said the mRNA ones should be good here, because your own body produces so much of the lookalikes that even a weak immune system should notice it - and then you're much better prepared to fight the real thing off faster.)

Only the first is immediately dangerous, so the standard seems to be to just stay away from those.

I'm not sure if much is commonly done for the second, in terms of looking for response, but you can get tests for measles antibodies and such, so that would probably be how?

The MMR vaccine has live virus, and before injecting the kids the nurse make a few additional questions about the health of the children and IIRC about the people that live with the children. (Like: Does someone in the family have cancer or is immunosuppressed? I don't remember the details.) It's safe, but they must check that the nearby persons are healthy.

High-risk populations such as the immunocompromised are tested in a Phase 4 trial.

That's true in general but I'd be very surprised if an inhaled rather than injected vaccine that didn't use any adjuvants or live virus was going to cause a serious problem.

Pretty sure omitting adjuvant would probably tolerize you to the peptide, which means you'd be more susceptible to COVID.

The goal of the vaccine is to train the immune system to recognize the real virus when it shows up. If you get it wrong, the vaccine may not simulate the virus very accurately which can lead to a number of issues. You may not mount an immune response when the virus shows up, or worse the vaccine may have improperly trained your immune system and you create antibodies that are ineffective against the virus but wreak havoc on your body. This has happened before with vaccine candidates like RSV or Dengvaxia. It can be deadly.

That's not even getting into the issues that may arise from skipping all the GMP/GLP guidelines. They can be tedious but exist for a reason.

Well, a vaccine is a rather vague and generic term. Are you talking about an FDA approved product? An experimental vaccine? A vaccine whose use is contra-indicated for certain people? etc. etc.

If I may - perhaps one alternative question is "Can an unapproved vaccine product cause harm?". With that re-wording, the answers become a bit more clear. Yes, chemicals used in the formulation maybe toxic, or the final vaccine might give rise to an auto-immune response, or could induce anaphylaxis in certain people. There could be cell debris/endotoxins that a purification process doesn't remove properly and causes problems. Maybe the vaccine contains an attenuated pathogen that can "revert", etc, etc.

Some vaccines in the past have been withdrawn for causing autoimmune disorders, eg arthritis.

For vaccines in general, i imagine it depends on the type a lot. Live vaccines for example have the obvious risk factor of maybe giving you the disease, but i dont know much about the topic.

I imagine for this article the biggest risk is you make something other than you expect and poision yourself, or you just make something that does nothing. (IANAexpert)

You can actually do much worse than nothing with antibody dependent enhancement. Let's say you make something that at first glance appears similar to the virus but is a little off. Maybe you chose the wrong proteins, or maybe you used an inactivated virus and the inactivation step damaged some key part of the virus. You inject the vaccine and your body learns how to make antibodies for this particle.

Now the real virus shows up, your body goes "Aha! I've seen this before let me make those antibodies." But it wasn't trained on the real virus, so the antibodies it makes aren't actually effective against the real thing. The virus replicates and your body makes more and more antibodies but they do nothing to stop it. Meanwhile the the antibodies are running rampant in your body causing inflammation and blood clots.

This has happened before with vaccine candidates, and is analogous to what goes in on severe covid. The body tries to respond to the invading virus but does so ineffectively and causes potential deadly damage.

Isn't it possible your body would have the same response if it was exposed to a variant of a virus that it already has antibodies for?

Maybe the explanations are simplified but I don't quite understand how the immune system could fail to recognise permutations of proteins or any other differentiating factor between COVID-19, its variants and mRNA vaccines; nor what makes this specific example of vaccination riskier.

For a real-life example look into dengue fever. There are multiple variants that - to our immune system - look very similar, but antibodies for one do not protect against the others. This means that if you recover from one variant and are subsequently infected with a second you can have a really really bad time.

The reason the second infection is so bad is exactly as outlined above: your immune system 'recognises' the second variant and produces antibodies that it learnt when fighting off the first variant you recovered from. Unfortunately, these antibodies are useless against the second variant, and you have a bad time.

This exact same issue happens with the current vaccine for dengue, which is why it is only given to people who have already had dengue of some kind, or in populations where most people have had it before. For a situation where this did not happen see the section titled 'Phillipines controversy' in the wikipedia article.

There is currently a lot of work being done to produce vaccines that protect against all 4 variants at the same time, with some promise for the years ahead as trial results come in!

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

Your immune system is not intelligent. Through natural selection it has evolved to be able to handle some things, but it can't see permutations like that, as they are not something it evolved for, it's all chemical/physical matching.

I think he was referring generically to any bad crafted vaccine. Not the one approved by authorities. Indeed any improvised drug can be harmful.

https://www.washingtonpost.com/history/2020/04/14/cutter-pol...

Something like that advice would have been good for Ben Franklin too. And Marie Curie. Some people want to survive and some people want to be heroes.

Those people tested their theories, did experiments. They didn't just stick something up their nose and assumed it worked with no further investigation.

I believe GP is trying to conjure up images of flying kits in thunderstorms or walking around with radioactive material in your pocket.

> They didn't just stick something up their nose and assumed it worked with no further investigation.

Good thing that's not what the article author has done, ey?

But it is. The author has made no attempt to test whether he is immune to covid as of this writing. He talks vaugely about future blood tests, but its unclear what test specificly, if a positive result would actually mean he is immune, if a Negative test would mean he is not, so its basically a test that tells us nothing, and he hasn't even done it yet.

If your experiment is not falsifiable, you are not doing science.

He explicitly has not "assumed it worked", nor has there been "no further investigation" (there has been some and will be more).

Both parts of the great grandparent's sentence are false. I don't think saying false things for rhetorical effect is good for the health of hackernews discourse.

I maintain my statements are neither false nor are they being made purely for rhetorical effect.

I do think context and implication do need to be taken into account when evaluating the authors statements. The authors present this article as if they were making an actual vaccine. They talk about how you too can make one. With strong implication that its likely to do something. Admittedly, they do talk about follow up, but its follow up that by their own admission is not likely to show anything, and that's after having an incredibly rosy view of it, to the point where i don't believe anyone could reasonably call it a follow up.

As far as healthy discussions go, i would say that assuming the people you disagree with are arguing in good faith and while they might be mistaken, ultumately believe their premises and not simply intentionally making false statements to further their rhetorical point, is important too :)

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