Making Vaccine

The main answer here is "see the paper"; there's a lot of discussion about this stuff. I'll summarize a few points, as I understand them, relevant to your particular thoughts.

• The "snorting chemicals" aspect is generally not much of an issue, since every ingredient other than the peptides is food-grade, and the quantity in a dose is tiny (one dose is <1 mL, and most of that volume is vinegar and water). If you were eating this stuff in your food and coughed on it, you'd probably get a higher dose than what's in the vaccine.
• Peptide synthesis services generally provide various quality control checks on the product (some free, some upcharge). So at least you'll know what you're getting.
• Antibody-dependent enhancement is one of the main things the paper discusses. It's pretty rare to begin with, and the cases where it's happened have some patterns to them which can be avoided; the peptides are chosen to avoid those pitfalls. Reading between the lines, it sounds to me like historical cases were largely a by-product of historical vaccine techniques (e.g. attaching pieces of one virus to the backbone of another in the case of Dengvaxia) which aren't used here.
• As I understand it, interfering with administration of a later vaccine while also being ineffective would involve basically the same pieces as antibody-dependent enhancement. The paper did not specifically discuss this, though.

From a risk perspective, the fact that this is intranasal rather than injected makes it feel safer to self-administer, I expect, but is that feeling really justified?

Tongue-in-cheek answer: I'm generally pretty comfortable snorting small amounts of things which go in food; this sometimes happens by accident when eating anyway. Injecting small amounts of things which go in food, not so much.

More seriously, all sorts of shit goes into our noses all the time. The blood depends more on being kept separate from the outside world.

[W]hat are the risks involved in creating substantial immune effects in my body using a thing I found on the Internet, which has received comparatively very little testing, and without enough knowledge to really verify any of the claims myself?

This is one of the great challenges of Rationality: you need some level of expertise yourself before you can distinguish real experts from fake [LW · GW]. There is no substitute for learning at least some amount oneself, and thinking through the gears oneself.

I think a lot of these questions are answered in the radvac paper. I sent a copy of it to a biologist I know, and asked if he thought it was crazy to do this, and he read it and said “geez this looks safer than doing drugs”. I don’t have enough expertise to add anything beyond that.

@Davidmanheim you're a pretty big outlier here, and this is also the kind of question where I'd trust your judgement a fair bit: 

So curious if you wanted to elaborate a bit on your model?

This was great.

> The radvac vaccine will have serious side effects (i.e. besides stuffy nose for a day) for >50% of people who try it

It should be well below 1%. Firstly, if it were that bad as to cause serious side effects for >50% of people who try it, would the RaDVaC team risk promoting it? Secondly, if it were that bad, wouldn’t we hear bad stories about side effects? Thirdly, getting serious side effects accidentally in >50% cases sounds pretty hard on its own.

> The radvac vaccine induces antibodies detectable in a standard commercial blood test in most people, using the dosage in the paper with 2 booster shots

<1%, because RaDVaC team has tried it and didn’t manage to get any positive result.

> The radvac vaccine induces antibodies detectable in a standard commercial blood test in most people, using "more dakka", for some reasonable version of "more dakka"

This greatly depends on what “more dakka” and “reasonable version” means. I assume that “reasonable version” implies "doesn't cause too much harm due to immune system overstimulation”. If “more dakka” means simply a higher dosage, then I think, that this is unlikely (5%), because 1) RaDVaC team experimented on themselves quite a bit, they received a lot of dakka, but no commercial blood test detection, 2) RaDVaC team seems reasonable enough to try this approach if it looked promising. If “more dakka“ includes stronger adjuvants (chitosan is considered a weak, but safe one), then it is much more likely (20%?), because RaDVaC team didn’t investigate those (for a reason) and it sounds plausible that you can get an immune response by irritating the immune system really, really strongly.

I would prefer "immunizes against COVID-19" to be better defined when asking the question. Immunizing against becoming systomatic with COVID-19 is a different value then immunizing against not being infectious with COVID-19 and both of those matter. Preventing rate of hospitalization and rate of death would also be important. 

I didn’t mean to predict on this; I was just trying to see number of predictions on first one. Turns out that causes prediction on mobile

I think what you have done here is re-invented the actual helpful version of a practice whose authoritarian bureaucratic cargo-culted version is called "anonymous peer review".

It is easy (and maybe dangerously wrong) to come to the straightforward conclusion that peer review in general is simply evil bullshit... until one finds the place from which a benevolent truth-oriented human (like oneself) finds a reason to consult with an actual "epistemic peer" as a prudent and socially-embedded response to one's own uncertainty about things one cares about.

I talked this out with a consultant friend who got his BS in biology. Here's what we came up with.

A conceptual solution would have the following variables, labeled for clarity.

Cost of vaccine = C

• C = (Cost of manufacturing RacVac) ÷ (Doses you'll administer) + (Dollar value to represent cost of unconventionality of the project)

Probably that vaccine provides value = P

• P = (Chance that RadVac works at all) x (Effectiveness if it does work) x (Chance you'll catch COVID before getting vaccinated) x (Chance you'll fail in your execution)

Value that could be provided per person = V

• V = [ (Dollar value of your life) x (Chance you'll die if you catch COVID) + (Dollar value of avoiding a day on a ventilator) x (Chance of serious case of COVID) x (About 14 days on a ventilator) + (Dollar value of avoiding a day of fatigue/anosia) x (Chance of long-term fatigue/anosia) x (Expected length of long-term fatigue) + (Expected number of days out of work) x (Cost of lost work) + (Expected out-of-pocket cost of medical care if you caught COVID)]
• P' = 1 - (Chance you'll transmit it to a particular other person if you catch it) x (Chance they'd have caught it anyway)
• V' = Calculation of V but for another specific person in your life who'd be at risk of COVID if you caught it

If C < P[V + ΣP'V'], it would be worth taking RadVac.

Potential sources for some of these estimates:

• (Chance that RadVac works at all) = (Number of vaccines major pharma companies send to preclinical trials) / (Number of vaccines they put in clinical trials) x 33.4%
• (Effectiveness if it does work) = (Average effectiveness of mRNA vaccines that have been released so far)
• (Chance you'll catch COVID before getting vaccinated), (Chance you'll transmit it to a particular other person if you catch it), (Chance they'd have caught it anyway) = Calculated by adding up your own and other people's activities using the microCOVID risk calculator.
• (Dollar value of a life) = (Dollar value placed on a citizen's life by their federal government)
• (Chance they'll die if you catch COVID) = Hospitalization and death rates by age
• (Chance of lingering effects of COVID) = 52.3%

However, you'd first want to consider if there are other interventions that are even more cost-effective for the same risk factor. For example, if you're still shopping at the grocery store, consider having your groceries delivered for the next six months.

Hmm, important as in "important to discuss", or "important to hear about"?

My best guess based on talking to a smart open-minded biologist is that this vaccine probably doesn't work, and that the author understates the risks involved. I'm interpreting the decision to frontpage as saying that you think I'm wrong with reasonably high confidence, but I'm not sure if I should interpret it that way.

In my case, yes.  My bio expert indicated that it was likely to be effective (more than 50%, but less than 90%) and that the risks were effectively zero in terms of serious complications.

Regarding the food grade versus lab grade question, as well as inaccuracies or mistakes in construction of the vaccine, this was a question I spent a reasonable amount of time on.  The TL/DR is that the engineering tolerances are incredibly wide; the molecular weight of the chitosan isn't that important, the mixing rate isn't that important other than it be fast enough, the quantities aren't that important, exact peptide quantities aren't that important etc.  A lot of these can be off by not just percentage points, but integer factors, and the result will still be acceptable.

It's also worth pointing out that unless you make serious, significant mistakes that dramatically impair effectiveness, you can always just use "more dakka" to overpower the variations.  My plan is to mix each batch independently, such that at least some of the construction variations are expected to cancel.  (Also, freezing the final vaccine is likely to impair effectiveness, from what little I've found on the topic.)

I did not try this test. I had enough bio and physiology background to be confident in my own assessment, though I would not advise others to be similarly confident in my assessment - my background is not legible enough for that.

If (!) these instructions are exhaustive, it might be easier, though possibly more expensive to produce than RaDVaC.

You need to work a lot more sterile when injecting then when you spray something in your nose. I'd rather have a few additional steps with less problems if I mess up some of the steps.

Thanks for posting this, this looks excellent.
It's my impression that you can indeed just buy the antigen needed - the lowest price for 1mg I found was around 900€. Allowing for 10% waste, this would cover 20 individuals at 45µg each. I looked at the antigen test results first and was worried that the vaccine wouldn't perform as well in live tests, but the neutralization results Stöcker posted are quite promising and a Nature study suggests that using 319–545 of the RBD is effective in providing immunity to live virus in primates. I don't expect the remaining amino acids will affect the results in a major way, so this looks quite promising indeed.

I've asked a few people with more domain knowledge to comment on this and depending on their judgment (and access to sterile lab space) I might fund vaccines for myself and friends, given that Germany's vaccine rollout seems to be taking its time.

I think deleting it was a fair response (though perhaps banning is a little over the top). assuming the moderator has no way of checking for himself whether this makes sense and he knows he doesn't, he's left with a bet about whether this is the real thing or just bullshit. he expects more bullshit than real things, and he expects the bullshit to be dangerous. so he removes everything that fits this class of things, knowing he might end up also removing something real.

I wouldn't look too deeply into that. The selection process for moderators on reddit is essentially first come first serve + how good are you at convincing existing moderators you should join the team. As far as I can tell this process doesn't usually select for "good" moderation, especially once a sub gets big enough that network effects make a subreddit grow despite "bad" moderation. This applies for most values of "good" and "bad". 

This article from July 2020 claims that George Church and many of his colleagues had already self administered their vaccine at that point. It's almost certainly true that there hasn't been a clinical trial, because nobody has ever had an incentive to run a clinical trial. I don't think their intent was to publicize this widely or profit commercially from it. Rather, they realized they could just do it, went ahead and did it, and wrote up their findings publicly but under the radar, so other like-minded individuals could duplicate their procedure at their own risk. Remember that they are an academic research group and they face very different incentives than the drug companies trying to vaccinate the general public. In any case, it seems clear that these vaccines have been tested on many living things, just not in an official study.

I'm afraid I'm not flexible enough to kick myself that hard.

Regarding the 33.4% approval rate:  based on what I've learned about traditional vaccine development and production in the last few months, I am not at all surprised.  Both peptide and RNA vaccines are effectively "state of the art" technologies compared to traditional vaccine techniques.  It's like comparing modern non-invasive out-patient surgery to the 1970's equivalent.

You need look no further than the russian and chinese vaccines - those use the rather crude technology of "throw big chunks of inactivated virus particles at the immune system and hope that the immune system guesses the right antibodies to deal with the live version."

Both peptide and RNA vaccines are instead, "we have identified very specific antibodies which we know are effective both from the serum of recovered patients and from computational modeling, then use exactly the minimal protein sequences needed to generate those antibodies."

Both the russian and chinese vaccines use chunks of proteins that are thousands (and likely tens of thousands) of amino acids long, in a mostly inactivated form.  The immune system has no idea what to latch onto, what will be effective at stopping replication, but it does generate a bunch of randomish antibodies anyway just in case.  In a lot of people, this is enough to take the edge off getting stick.

The peptide and RNA vaccines on the other hand, are extremely narrow.  The radvac vaccine for example targets 9 specific virus protein sequences, the shortest of which is 10 amino acids long, and the longest of which is 25.  Each of these sequences is from an empirically likely effective antibody, found in real people who have really recovered.

Like I said, very, very different technologies.

Vaccines that are brought to clinical trials

This is an inappropriate reference class. This has no in vitro testing conducted; it's entirely a computational model. "“Peptide” just means “sequence of amino acids.” Would you conclude that, because some lines of code can navigate a rocket to the moon, that your code is pretty likely to navigate a rocket to Mars?". A vaccine brought to clinical trials has already overcome many more hurdles than this has. Generally in vitro testing (I think both for safety and efficacy), in vivo safety testing (in rats!), and some scaled-up testing in other animal models.

This isn't a vaccine candidate. This is a promising research lead for a vaccine candidate.

You're missing the very real possibility of long-term negative side-effects from the vaccine, such as triggering an auto-immune disease or actually increasing your susceptibility, both mentioned in the whitepaper (whose risk-assessment I would be pretty sceptical of). I would think of this as more a trade-off between risks of side effects and COVID risks, rather than whether or not you can afford it.

Vaccines that are brought to clinical trials have a 33.4% approval rate, which seems like a reasonable estimate of the chances that this vaccine works if executed correctly.

I don't follow. Don't vaccines have trials on cells, mice, primates, before clinical? So unless radvac has also done similar testing, this 33.4% isn't comparable.

Do you value your life at ten million? As in, would you take a 50% chance of death for five million? If so, why are you not smuggling drugs or whatever?

My understanding is that it helps a lot.

The biggest benefit seems to be that the immune system is primed in at least some fashion; it knows what to look for, and it has readily available tools that should be effective.  It doesn't have to take a day or a week to try random things before it finally discovers a particularly effective antibody and gets the production chain ramped up to start a proper immune response.

Instead, your immune system will very quickly get a signal it understands as bad and can immediately start ramping up when it does detect the virus.

Keep in mind that the commercial vaccines don't have 100% success rate in that some people still get sick, but the 'priming' of the immune response is still there.  I believe this is why the death rate / severe complications rate is effectively zero for immunized patients, even though it's possible to get sick.

(Again, my understanding.  I would very much appreciate correction/clarifications here.)

The way the tests we've used work is a nurse takes a blood draw, then ships it off somewhere for the antibody test, so there's not really an opportunity to use mucus in the test. If the next test comes back negative, then I might search harder for an at-home antibody test and a protocol for mucus.

Ah excellent, thank you for getting ahold of someone. This matches the qualitative impression I had from the white paper.

It's not clear from that comment what the denominator is - i.e. 4 out of how many who tested for it? The white paper says that about 100 researchers had taken the vaccine (most of them presumably not as early as May/June), and the comment says "only a handful" were collecting samples rigorously as of May/June, so I'd guess ~10 or less. That gives ~40% chance or higher of antibody response with that version of the vaccine (where "or higher" includes a significant chance that only 4 people ran the ELISA assays, in which case Laplace' rule would give 80% chance of antibodies). Though note that the current version focuses on a different immunity strategy so it may not generalize, and the error bars were pretty wide to begin with.

One thing to note: if there's an antibody response in a significant fraction of people but not everyone, that's exactly the world where I'd expect "more dakka" to work.

YES. Man, the most annoying part of this is you spray the stuff, and then have to spend an hour+ with your nose feeling runny but not blowing it.

Oh, it's far, far worse (better?) than $2 per dose.  As a thought experiment, I price estimated buying enough peptide for a hundred thousand doses, and it only costs about ten thousand dollars.  Ten cents a dose is closer to realistic if you buy in bulk.

Which also brings to mind a question of civilizational inadequacy:  if we really cared and it really mattered, why not have every university with a lab in the country crank out a hundred thousand doses per week to their local populace?

If the thing your making exists and is this cheap then why is Pharma leaving the money on the floor and not mass producing this?

There are a number of costs that Moderna/Pfizer/Astrazenica incur that a homebrew vaccine does not. Of the top of my head:

1. Salaries for the (presumably highly educated) lab techs that put this stuff together. I don't know johnswentwort background, but presumably he wouldn't exactly be asking minimum wage if he was doing this commercially.

2. Costs of running large scale trials and going through all the paperwork to get FDA approval. I think I'm generally more in favour of organisations like the FDA than a lot of people 
here, but even I expect this to be a very non-insignificant number.

3. Various taxes and costs of shipping/storing the vaccine until it can get to customers.

4. Costs of liability and a desire for the company to make a profit on this (as well as to pay the salaries for the all of the people needed to keep a large company running).

Given all that I don't think the gap between this and the commercial vaccines is that insane. 

why is Pharma leaving the money on the floor and not mass producing this?

Both the other comments here are on-point. The materials for large amounts of radvac would cost pennies per dose, because the cost-per-unit of the peptides drops very rapidly as you scale up (remember, we doubled our order for <10% extra cost).

However, in general, people and logistics are a bigger expense than materials for most products these days, and I certainly expect that to apply to vaccines.

As someone else said, the logistical difficulties for this are much larger than the standard jab method, the production process doesn't scale well, and once prepared it doesn't last long even if you freeze it. Making this for 20 friends and distributing it to them is very plausibly net-harmful, because you need to gather in close quarters to hand off the prepared vaccine, do it within a fairly short window (1-3 days) for all 20, and then repeat all that, including the production of new doses, at least once per week and ideally 2-3x per week. Given that the only evidence for efficacy is in silico, none in vitro let alone in vivo or in actual humans, it's not at all clear that the benefits outweigh the increased risk of spread from all that close contact.

That's only for raw materials.  Actual production seems to have involved a fair amount of skilled labor per dose which probably dominates the $2 figure.  A commercial vaccine can automate that but then you've got lots of development costs as well as logistics and compliance to worry about.  I wouldn't expect that this vaccine is especially cheap.

Welcome, and thanks for making your first comment!

As a fellow scientist with decades of experience in the industry, I disagree with several of your claims.

First, you will never know if it really works until you run blinded clinical trials against a placebo. This is the only way to tell and that is why it's required for any new drug/vaccine to be launched on the market. 

Clinical trials are helpful for understanding whether a drug/vaccine works on the population level. But on the individual level, clinical trials are not the only way to tell. For example, you can just take an antibody test and see if it works.

You can't just take a antibody test and see if it works.

Of course you can.

Even if there were the right antibody tests for these peptides

Anna Czarnota posted an initial protocol here [LW(p) · GW(p)]. I haven't tried it, but it seems reasonable and likely to provide useful information about one's level of protection.

but without using rigorous scientific method, there could be many other factors why you could see a response. Like you were exposed already to the virus and didn't know it.

The "rigorous scientific method" is not the only way to generate knowledge that allows individuals to update their priors. But setting that aside, the question of whether one's immune response came from the vaccine or from previous exposure to the virus is not very relevant to one's future decision making. Either way, the antibody test provides information about one's current level of immunity, which one can use to update their risk tolerance and behaviors.

It feels like your comments are aimed at the question, "What is the best vaccine (or vaccines) to approve and mass produce for the general population?" which is a perfectly valid and important question. As things currently stand, this relies on the standard clinical trials/FDA approval process. But this process takes a long time and is prone to all sorts of delays and inefficiencies due to politics and organizational maze behaviors, during which the pandemic continues to spread. Realizing that, the radvac developers and many commenters here have been asking a different question: "What can individuals do now (or in a future pandemic) to mitigate their personal risk of being infected?"

Both questions are important, but the large organizations responsible for developing/approving new vaccines have very different incentives than individuals looking for ways to minimize their own risk of infection.

This sounds to me like the kind of thing biology expertise to get right and potentially more equipment. 

My rough guess is that there's a 75% probability of effectively full immunity, and a 90% probability of severity reduction.  This is a pretty well tested and understood vaccine mechanism, and the goal isn't "perfect immunity" as "prime the immune system so it doesn't spend a week guessing about what antibodies it needs to combat the virus effectively".

As to why established companies don't do it, I believe it's partially logistics, and largely red tape. Logisitics first (though it should be noted that at least some of these could likely be tackled with a bit of effort):

• Shots are well understood and easy; people are used to them, people know how to give them, etc.  Nasal spray is irritating and makes you want to blow your nose, which washes out a lot of it and reduces effectiveness.
• You need multiple of these annoying doses in the nose, staggered a few days apart, to generate a 'good' response.
• This particular nanoparticle vaccine doesn't have a long shelf life due to peptide degradation.  Peptides don't last forever, and while they're more stable than the RNA vaccines, you'd have to ship them frozen as well.
• Nanoparticle vaccines in general suffer from particle aggregation over time.  The particles will gradually aggregate in solution, and if you freeze it they aggregate faster; freezing changes the size distribution pretty dramatically.  That said, I don't know how much that impacts effectiveness, and it doesn't seem like an extensively researched topic.  I only found one paper discussing it.
• Because it doesn't have a long shelf life, it has to be mixed in-house, then distributed, preferably within a small number of days.  I plan to mix a new batch every week for my prime and boosters.  On the plus side, mixing it can actually be done at home with pretty cheap and ordinary tools, it just takes time.

Red tape on the other hand is a huge problem and flat out intractable.  Unlike injections, companies need to get safety approvals and testing done for pretty much all the components and the delivery mechanism, not just the active ingredients (the peptides.)  Then, separate approvals and testing for each individual set of peptides, via a process that operates closer to the scale of decades than months and costs billions of dollars.  Any modification to the peptide set can be expected to restart the process from scratch.  Then, companies also need to set up / reconfigure their legal strategy to protect themselves, and ensure that things are sufficiently balanced business-wise that they don't go bankrupt.

Using ancient, primitive "stab people in the arm" technologies isn't great, but it erases likely more than half of the regulatory burden, because "we've been doing that for a century and we know it's only somewhat dangerous", wheras new technologies like "snort some nanoparticles" are Scary and Dangerous and New and Have Not Yet Been Approved By Appropriately Serious People Being Serious.

Nevermind that every time you play with a pet, breathe in part of a cloud of dust, or smell your SO's hair, you're inhaling more foreign peptides than what's present in a vaccine dose.

I think the chances of side effects as serious as COVID are much lower than that. I also think the chances of success are higher, but on that front it probably makes sense for you to wait a few weeks at least until I, and possibly others, have some test results.

But my biggest difference from this calculation is that I'd account for the benefits of not-having-to-try-hard-to-avoid-COVID. The chance of catching it is only low if you avoid going out and socializing; with a successful vaccine, you can have a low chance of catching it without paying that cost.

So that's how my calculation would differ. On a meta level:

So I do not think, given my beliefs, that I should recommend it. Is this reasoning broadly correct?

... your reasoning is reasonable, and I do not think anyone should defer to my reasoning on this subject; I do not have enough legible expertise to merit that. Upvote for writing out the calculation.

I do not know the baseline for chances of a side effect in a new peptide vaccine. I expect that if side effects anywhere near as bad as COVID happened with any non-negligible rate, then I would have heard about it already, but I don't have numbers or data on it.

Huh. I believe we ordered from the labcorp website, didn't have any problems.

Cerascreen offers an at-home antibody test. You use the kit you buy to draw a small blood sample at home and mail it to them. They use the ELISA method to test the blood for IgG antibodies and show you the result on a webpage. Not sure if this is available outside Germany, though maybe a different company offers something like this where you live.

Abbott also produces a blood test for IgG/IgM antibodies, except that it comes with a small test cassette that gives you the result directly, without sending it to a lab. Maybe importing this (or something similar) is an option for you.

Does this add you to an email list where discussion is happening, or merely put you on a map so that others in the area can reach out to you on an ad hoc basis?

Just based on general background knowledge, if autoimmune problems were induced by sequences short enough to show up frequently from random noise, then we'd have autoimmune problems all the time (since we're breathing in peptides - including partially-broken-down-peptides - basically every day). So I'd be very surprised if it were an issue.

This is exactly the sort of question I love to see, though. Great thinking.

I don't know this, but the whitepaper does mention that this approach is quite common for research vaccines.

The whitepaper is a good source, but like johnswentworth, I also contacted a medical professional to evaluate it.  The response came back quickly and confidently, and was along these lines:

"Oh, yeah, this is safe.  Nasal vaccines are safe.  The biggest worry is that it might not work, so make sure you get the commercial vaccine too.  I'd be interested in doing this with you as a joint project and giving it to my family, and I also have a colleague who might be interested in doing it."

The biggest point of disbelief on their part was that it's possible to order all the equipment and peptides online and have them shipped to your door.

See the answers to gwillen above, and also the whitepaper.

Two things. First, death isn't the only downside of coronavirus. Even losing your sense of smell for six months sucks. (My mother caught COVID in March, and spent the next few months complaining that her food tasted like dirt.) And of course there's other forms of damage as well.

Second, and more importantly, control systems. The death number (in any age band) is low in large part because people are staying home and not socializing. The chance of death I would create for myself and those around me by going out and/or socializing is probably higher than 17/100k. The upside of immunity (in particular measurable immunity) is that I can increase my exposure without breaking the control system.

In my case, I'd estimate that I've spent around two hundred hours over the last several months coming sufficiently up to speed on the topics that I can reason about them.  I started with about your level of biology (or possibly less), but probably a slightly stronger chemistry background.

For the basics, I started with cell biochemistry, DNA/RNA, mRNA and protein construction.  From the vaccine side of things, I just started looking up things I found in the whitepaper which I didn't understand, and once I understood all the terms I started looking for and reading research papers. When I found something I wasn't sure about, I researched it and learned about it.

As examples, in early January, I spent about ten days reading up on VED (vaccine enhanced disease).  Shortly after, I spent a few days digging into chitosan, and trying to understand how sensitive nanoparticle creation is to changes in the mixing process (hint:  not very.) Everything I searched for I was able to find, and pretty much everything reinforced the same internally consistent view of the world.

When you find something that doesn't make sense and you're stuck, write it down, file it away and come back to it later.  Eventually you'll be able to make sense of it.

When you're able to read through most or all of the whitepaper and understand both what's being discussed and why specific things were selected, you'll be in pretty good shape.

It's not particularly difficult, it just takes time and effort.

That's a tough question.

To a large extent this project involves specialized knowledge about the immune system, and that's stuff which you just have to look up one way or the other. That part is pretty straightforward. Same with looking up random jargon; that's a part of any biology research.

The harder part is the not-very-legible general intuitions about biological systems - e.g. things like "a <25 amino acid peptide isn't likely to have any function as a protein in its own right" or "error bars are on a log scale, and probably wide". If you want to acquire those sorts of intuitions, one relatively-fast path might be the bionumbers book.

On the other hand, even without those intuitions you could just brute-force your way through by checking everything. For instance, if you don't have the intuition that error bars are wide and on a log scale, you could find a paper experimentally measuring the concentration tolerances for chitosan nanoparticle formation. In some ways that's better - you're less likely to miss things and you can end up a lot more confident in your assessment - but it's a lot more work.

In addition to this, the current version of radvac was designed to be more robust to mutations on its own. Specifically, it targets some non-spike/RBD parts of the virus, which are more evolutionarily conserved. And of course simply having an immune response to a different part of the virus than the large population of mainstream-vaccinated people is itself helpful, since mutations will be selected to circumvent the most common immune mechanisms.

Nothing unusual that I've noticed. A bit of congestion a few hours after taking it is expected, but air quality is not great here so I'm mildly congested pretty often anyway.

I'd be very curious to see a protocol for this.

No, they ship dry.

So...is the process to simply identify some suppliers (not hard to find with Google) give them the amino acid sequences in the instructions and ask for a quote?

The one I used had an online "custom peptide synthesis" order form. I just pasted in the sequences, checked a few boxes, it autogenerated the price tag on checkout screen, and then I hit the order button. (It actually took a bit longer than that since both my girlfriend and I triple-checked the sequences.) I specifically avoided any suppliers which would have made me talk to a salesperson to get a quote - that crap is a strong sign of Maziness.

having taken this is there any concern about being required later to also take one of the officially blessed vaccines

Dentin had a comment on this somewhere in this rapidly-growing comment section, saying that the commercial vaccines use different epitopes and should therefore play well together with this one.

I think another John Wentworth post [LW · GW] is applicable here. It's not hard to invent reasons why any given post might increase existential risk by some amount. (What if your comment encourages pro-censorship attitudes that hamper the collective intellectual competence [LW · GW] we need to reduce existential risk?) In order to not function as trolling, you need to present a case for the risk being plausible, not just possible.

Is this blog post potentially a source of X-risk? Popularizing the idea of "mix together chemicals you got in the mail" sounds like an attack vector for an AGI wanting to escape its box.

No, an AGI would already have to escaped it's box to take over companies from which you can order chemicals and sent out what it wants. From there it can simply pay people to do what it wants. EmeraldCloud Lab also exists and could mix out what the AGI wants. Plenty of people take drugs they order on the Darknet.

That's only an issue if the low effectiveness vaccine mainly targets the spike protein and targets it in ways that the vaccine can mutate out of. 

In contrast to the approved vaccines this vaccine is designed to make it harder for the virus to become resistent to it. 

Identifying the right short snippets takes time, while using the whole protein is simpler and more likely to work. 

If you identify snippets that are conserved over evolutionary time, it's harder for the virus to mutate in a way that it becomes immune to your vaccine. 

Specifically, the ultimate purpose of a vaccine is to get protein into the body. 

That sense got me to write my last post [LW · GW]. I think there's some hope that bringing the vaccines into cells in the body produces a slightly better immune response then having them in blood and giving an adjuvant.

If it's so cheap and easy to make vaccines, why aren't commercial ones made this way? 

That might be the "why does nobody prescribe melatonin"-question that Scott Alexander discussed. You can't patent "we target the spike protein" as that's the obvious thing that everybody is doing. 

In particular, the Novavax vaccine sounds similar, so why wasn't that the first vaccine to market?

It seems Novavax spent more time testing different variations before deciding that using the spike protein as everybody else is the way to go.

As far as I understand they also ran their own clinical trials while Moderna and BioNTech got external help running the trials which might made running the trials faster. 

The cost of peptides is probably super-linear in length.

This seems to be true for the amount that needs to be produced to do biology at home. If you however optimize hela cells to produce a given protein and then just let them doublicate this gives you proteins that are cheap enough if you do things at scale.

I predict that is an overly-optimistic reason for why they're rejecting the vaccine.

My personal estimate is that the the percentage of nurses who have done this is effectively zero (less than one in a thousand with high probability, less than one in ten thousand with moderate probability.)

Further, those who did do it are likely to have read through the whitepaper, and therefore are also likely to get the commercial vaccine, as it covers different epitopes than the radvac vaccine.

This is a conversation with an MD I recorded which may answer some of the reluctance:

tldr; An untested delivery mode scares an MD to think that neurodegenerative diseases will increase in vaccinated.

I think lipid nanoparticles may have too broad a tropism, far broader even than attenuated virus vaccines (which are still limited to the tropism of the wild-type virus), and thus could pose a uniquely high safety hazard due to cytotoxic attack on the broad cellular range that uptakes the LNPs. Since the LNPs would enter cells via endocytosis, the SARS-CoV-2 epitopes would be expressed on MHC-1 molecules, making them targets of cytotoxic CD8 lymphocytes, attacking a much greater range of cells than any previous vaccine modality. This is concerning in general, but it’s a nightmare scenario if the vaccines are crossing the blood-brain barrier and endocytosing into e.g. oligodendrocytes (multiple sclerosis risk) or motor neurons (which could possibly cause an ALS-type picture). No other vaccine has this broad tropism. That is THE major safety concern here.

1. Because of the anatomy and circulatory trajectory from the deltoid and cephalic vein (essentially a straight shot into the SVC), if enough “spillover LNPs” are getting shuttled into the right atrium and transiting through the pulmonary circulation — which could be high, another reference here for the rich vasculature around IM injection — then one of their earliest stops on the map after exiting the heart would be in tissues serviced by branches of the common carotid and subclavian arteries (including the CNS), enhancing delivery to tissues behind the blood-brain barrier simply due to higher relative concentration at tissue corridors more proximal to the injection site.
2. Even if initial transit through the BBB and into other sensitive tissue parenchyma is relatively low, there’d be a cumulative effect with each booster delivering more spillover LNPs to those non-local sites.
3. Related to that point, the duration of immunity is still unclear, and there seems to be general agreement that while COVID-19 symptoms are reduced with the immunization, viral spread is not. If antibody and memory B/T-cell levels wane within a few months after vaccination, then we’d be looking at repeated boosters possibly multiple times a year given ongoing community dissemination. And since the development of many e.g. CNS disorders is gradual — with subclinical issues taking shape over years before clinical manifestations become apparent (as seen in MS and ALS) — such cumulative damage likely wouldn’t raise red flags at first, but could increase in likelihood with successive boosters.

Given that this vaccine targets a different part of the immune system there's no good reason to reject an injection vaccine when you take this vaccine. 

This seems prima facie unlikely. If you're not worried about the risk of side effects from the "real" vaccine, why not just take it, too (since the efficacy of the homemade vaccine is far from certain)?. On the other hand, if you're the sort of person who worries about the side effects of a vaccine that's been through clinical trials, you're probably not the type to brew something up in your kitchen based on a recipe that you got off the internet and snort it.

At this point in the game, things like "advancing knowledge" and "I really want to know if it was actually this easy all along" are at least as big a factor as the object-level benefits. If this were last July, or if I lived in Europe, then it might be a different story, but at this point I'm likely to get vaccinated within a few months anyway.

On your specific points:

a) COVID still sucks, I don't want my food to taste like nothing for six months, etc, but I'm definitely not at any significant risk of death from COVID.

b) I definitely do not expect that sleep/exercise/vitamin D/etc would achieve anywhere near the degree of risk reduction that a vaccine provides, and I do expect preventative to be way better than treatment here.

c) I certainly would not consider "vaccine experts" reliable, as a category. I do think that I am extremely unusually good at distinguishing real experts from fake. Indeed, there's an argument to be made that this is the major thing which we should expect rationalists to be unusually good at. In the case of RadVac specifically, I think it is considerably more likely to work than a typical vaccine trial, and typical vaccine trials have ~40-50% success rates to start with (the highest success rate of any clinical trial category).

d) Not sure what you mean by this one. Sounds like you're making a generalized efficient markets argument, but I'm not sure exactly what the argument is.

e) Antibody test results would be the goal here. Though in practice, most governments seem so incompetent that they're not even actually looking at antibody test results or vaccination, so it's not a very large factor.

Please name those reasons instead of vaguely alluding to them. The above post and many other writings on LessWrong address some of the most commonly made arguments for why there is indeed not a particularly good reason for the incredibly slow process of the FDA trial system. I would be glad to hear more arguments, but am not very excited about vague allusions without any substance.