‘AeroNabs’ – Inhalable Protection Against Covid-19
ucsf.eduIt's really annoying that press releases tend to overhype research so much. As far as I understand from skimming the paper, they created a synthetic antibody against the Spike protein of SARS-CoV2 that binds very tightly.
There is no clinical data in the paper, they measured how tightly the nanobody they designed binds to the Spike protein and they did some neutralization assays against SARS-CoV2.
The advantages of the nanobodies compared to full antibodies sound interesting, for sure. But this is still a paper pretty solidly in the basic research area, and quite far from clinical use.
I found an article about this research that puts it into a bit more context:
https://www.statnews.com/2020/08/11/scientists-create-potent...
> While the lab results look promising, experts in the field advise caution because important work has not been done to test the compound in animals. “The critical thing is animal data. We’ve found things that are very potent in vitro that do nothing in vivo,” said Dimiter Stanchev Dimitrov, a professor of medicine who directs the Center for Antibody Therapeutics at the University of Pittsburgh and has created antibody-based therapeutics for numerous viruses including SARS and MERS, two other coronaviruses. He said it can take months to collect the needed data in animals. “Once these are tested in animal models, then I can get excited.”
Normally I agree that press releases way oversell the research, but I don't think that was the case here. Their camelid nanobody approach seems to be a fairly novel idea with some nice benefits over traditional antibodies, and most of the linked article actually does a nice job of walking you through the figures in the preprint.
Sure there's not any clinical data, but they actively admit that and I'm sure that's something they're working on. Furthermore, there have been multiple Nature papers published on SARS-CoV-2 neutralizing antibodies and antibody cocktails that use the same experiments (e.g. Vero cells) without testing in animal models or in humans. One step at a time!
Camelid nanobodies aren't that new, but this is still overselling stuff. I don't like reporting on preprint in general, and this article really doesn't explain the complexities of actually getting some early stage technology like this approved and developed. That's where you end up with the constant barrage of "oh look, another biomedical technology we'll never hear about again" comments, and the amount that this article tries to sell the tech in the headline and article really overstated the readiness of the tech and the near term impact it could have
If you take it as science reporting, mainly intended to be of interest to scientists or to people who follow the progress of science, then it's sensible. It's similar to the materials-science reporting they do for battery technologies.
These releases coming from University PR departments (this one's from UCSF) aren't really supposed to make it into newspapers for wide consumption. Their target audience is:
1. the people working in the same field—in other Universities, or in industry—who maybe don't have time to read journals, so you've gotta get their attention actively with a "billboard" announcement, rather than putting it in a journal they have to explicitly decide to read;
2. the people who fund the university, who want to see what sorts of neat things their money is being spent on.
Pop-science journalists sometimes glom onto these releases and make them more than they are, "retargeting" them for public consumption. You can certainly object to that. But as originally delivered, these publications are blameless for that.
I've never seen any scientists reading press releases instead of papers, they are certainly not targeted towards scientists. And you also don't have to read a full journal to notice an individual paper, it's quite common to have keyword-based alerts on Pubmed or something like that.
The level of detail in a press release makes it usually pretty useless to a scientist, it hides the important details behind language intended for non-scientists. The abstract of a paper is much more useful if you need to decide whether it is of interest for you at all.
I think you're right that the UCSF public relations team is doing neither hard hitting investigative journalism nor the sort of critical pre-Phase 1 analysis that prevents wasted effort in medical device development.
I enjoyed hearing about this new approach to infection control that is its infancy regardless. I felt a little hope for a creative solution to our current crisis and I didn't have to wade through the literature on camelid antibodies to do it.
New technology has always relied on a certain underlying optimism that you can do something that's new and better against the odds (since most fail).
Would you like this better if there was a disclaimer explaining in vitro/in vivo or just the long road from basic research to wide spread deployment?
The Statnews article I linked is a good example of reporting for this kind of very early result. It does clearly mention that this is at an early stage and that no clinical data has been collected yet. I think this is certainly interesting, it's just so tiring to see this kind of stuff turn up again and again in extremely misleading articles in mainstream media.
Though I think it would have been better to wait until peer review before making a press release. This is not a paper that has immediate clinical applications, and the peer review might still turn up some problems with the paper.
The article reports on the in vitro results and says they're going to be doing further validation in vivo. As I mentioned before, the same has been true for basically every other antibody being developed (monoclonals and ones isolated from patients), which were also initially published in Nature/Science/etc with only in vitro and structural data.
There are multiple aspects that are novel here: their size, the trimer (rather than a cocktail), and their stability/delivery. All of these seem worthy of reporting. They say they're about to start clinical trials to see if they could be efficacious; they don't say that they will.
> While the lab results look promising, experts in the field advise caution because important work has not been done to test the compound in animals. “The critical thing is animal data. We’ve found things that are very potent in vitro that do nothing in vivo,” said Dimiter Stanchev Dimitrov, a professor of medicine who directs the Center for Antibody Therapeutics at the University of Pittsburgh and has created antibody-based therapeutics for numerous viruses including SARS and MERS, two other coronaviruses. He said it can take months to collect the needed data in animals. “Once these are tested in animal models, then I can get excited.”
Since you seem well informed: does the research mention anything about use as an aerosol and why that might be considered before internal use?
They wrote that regular antibodies have to be given intravenuously. These nanobodies are smaller and more stable, so they argue that it is possible to use them as aerosol. The idea seems to be to use them as prevention, which would not be feasible if you have to inject them.
I can't really judge whether that approach makes sense, my experience is in the basic research area, not with clinical stuff.
Is the hypothesis of an aerosol as prevention that you could spray eg. an indoor area and prevent infected people who come into that area being able to infect others in an airborne way?
> In an aerosol formulation they tested, dubbed “AeroNabs” by the researchers, these molecules could be self-administered with a nasal spray or inhaler.
Right, but they do have the potential to also be used as treatment then? Considering they're easier to manufacture than synthetic antibodies.
Anyone remember the Benzites from Star Trek TNG? I guess we know what that gas they breathe in is for...
I know that this is a joke, but the gas they breath is supposed to be chlorine, moisture, and mineral salts to replicate their home world's atmosphere.
As far as I know, there's only one nanobody-based drug on the market today, caplacizumab, and it isn't administered through aerosols, but rather subcutaneously.
I know Ablynx was working on an inhaled one as a treatment for RSV, but I don't think it made it to the market (yet). This noveldelivery method probably needs lots of scrutiny from regulators before it can enter the market.
Looks interesting but so far only talks about using it as prophylactic via inhalation; however the virus is known to enter via mouth, eyes and anus as well (breaks in skin probably). Even so inhalation and touching to mouth are likely the most common vectors of infection, so seems promising.
It isn't the same thing (I hope!) but it reminds me of McIntyre Powder. Miners were told by their company to use a fine aluminum/aluminium dust they breathed in before going to work in a mine.
https://pubmed.ncbi.nlm.nih.gov/31532354/
"McIntyre Powder (MP) is a finely ground aluminum powder that was used between 1943 and 1979 as a prophylaxis for silicosis. Silicosis is a chronic lung disease caused by the inhalation of crystalline silica dust and was prevalent in the Canadian mining industry during this time period."
...and in case you were wondering just how bad an idea this was, it's been conclusively linked to Parkinson's: https://parkinsonsnewstoday.com/2020/05/14/parkinsons-linked...
It doesn’t have to be 100% effective for it to end the pandemic - it just has to be effective enough that it blocks most transmissions and gets the viruses reproduction rate under 1.
Well at the same time proving to not have any side effects, such as passage into the bloodstream followed by formation of molecules that the liver cannot break down and the kidneys cannot flush.
It's promising early research, but it's not even in laboratory animal trials yet.
Even if it worked exactly as advertised, how could permanently chuffing the Llama oil vape be more practical than masks?
PS: again if it worked exactly as advertised, could it be a tool to stifle incubation after a know exposure?
The virus is "known to enter" via the anus? That might be hypothesized by someone, but I haven't heard of any documented cases of anal transmission. Have you?
Here is one report[1] although this one is contracting it from the anus. Early in the pandemic I read about acquiring via the anus, but not sure if that was confirmed.
[1] https://www.cidrap.umn.edu/news-perspective/2020/02/studies-...
That's not what that report says. At all.
"Chinese scientists report evidence of an oral-fecal transmission route for COVID-19 viruses and show that, in hospitalized patients, viral RNA was found in anal swabs and in blood samples."
I.e. you find RNA in anal swabs & blood. It leaves your body that way. Which is a well-known fact, and might be very useful in population-level surveillance. It also means you should put the lid down before flushing, lest you create something lovingly known as a "toiled plume".
It does not mean you get infected via the anus.
Yes but I think inhalation is the deadliest route. I could be wrong though.
Anyone know about potential human immune responses to these?
That was my first thought as well, followed closely by "I wonder which interesting new cancer these might cause". Gotta love biomed.
UCSF is my alma mater but this wave of press about aeronabs is just ridiculous. This is research lab level work, far from the clinic. It should not even have been announced via PR, just publications.
It feels like a large amount of that research went into creating a marketable product name.
Oh great...
"Hey why aren't you wearing a mask?"
"No worries I'm using inhalable protection"
rolls eyes
Speaking of eyes I wonder if you can "inhale" it into your eyes too.
Viruses can enter the body more than just orally and even though we think it's primarily through the respiratory system, we aren't sure yet.
Even having expressed doubt, something is better than nothing. And if it eliminates requiring face masks it would be worth it alone for that.
I’m guessing any mucous membrane (eyes, mouth, nasal passages and I swear some other posts here said anus) is a risk but apparently lung cells are the most vulnerable
Won't this take too long to run human trials on for safety/efficacy for it to really matter? My understanding is that a vaccine will likely come out within 6 months or so. They mention that it's an older compound, but sounds like they made some novel changes to it. Since this situation is so much a race against time, we are probably better off focusing on older, better-understood compounds that don't need to be tested for as long.
A vaccine would be great, but it’s far from certain we’ll have one in 6 months. It makes sense to keep pursuing multiple lines of research.
A great vaccine still won't work for everyone. The biggest group being those whose immune systems are not functioning well, which depending on the vaccine could include a large chunk of the elderly most at risk.
It's very unlikely a safe vaccine will come out six months from now. It's even more insane to think most people around the world will allow themselves to be injected with something developed in less than a year.
Effective treatment will be much more likely to hit the market than a vaccine.
They offer it as a stopgap, which, I agree with you, seems improbable given the latest reports on vaccines:
Used once a day, AeroNabs could provide powerful, reliable protection against SARS-CoV-2 until a vaccine becomes available.
But maybe that's a signal that these researchers believe much of the vaccine news has been overly optimistic hype. I guess the race is on.
One question I don't think the article addressed: if successful, would this have applications beyond Covid-19? Like against the common cold?
That's really exciting. It reminds me of PrEP which is a pill you take that can prevent you from contracting HIV with like 99% success rate. It's really a game changer since there isn't an HIV vaccine.
I also don't want to get my hopes up since research like this is bound to be overhyped. I want to see where it goes like a month or two from now.
“Llama inspired design” is quite amazing for being a conscious design choice. It does look like a llama, but is that a good thing?
Are llamas in the UX toolkit as an animal that is both semi-exotic yet familiar enough to elicit positive reactions.
I encountered a bunch on Peru trails and they were pretty ornery (compared to yaks or sheep) and the 30 or so different Quechua locals I talked with said they were pretty bad as pack animals. So they seemed pretty normal to me and not really some cool animal.
This almost seems like someone testing a gpt-3 bot on HN...
Huh? They are not talking about some sort of aesthetic design. Llamas' immune systems use these short protein antibodies, which seemingly proved useful when artificially modified to block the virus. Nothing to do with branding.
I don't know if you read the sentence following that, but it's not about the apparatus itself:
"...inspired by nanobodies, antibody-like immune proteins that naturally occur in llamas, camels and related animals."
Is that a joke? The whole article is about proteins that can be found in llamas, nothing else.
You did give me a good laugh though.
This has to be a bot, right?
Not a bot, I think the inhaler looks like a llama and that’s what I meant.