> If we find that everyone who was infected with a particular deletion strain only had a mild case of COVID-19, then we have our candidate attenuated strain which could be used to accelerate vaccine development in a challenge trial.
Heavy emphasis on "candidate". How can you tell if people had a mild case because the virus had deletions or because they mounted an appropriate immune response? It's not clear that the vaccine will be protective.
I have addressed this many times before, but yes almost everyone with a mild case just has an immune system that is good at controlling the virus. This is irrelevant to finding an attenuated strain.
The real value of finding an attenuated strain (one that causes mild illness in everyone) is that it would be ethical to use it in a challenge trial of a conventional vaccine. The Oxford vaccine group for example are planning a large field trial because they don’t think it is ethical to expose people to the normal dangerous strains. If we found an attenuated strain we could speed things up massively.
Ignorant question: is it possible to have something resembling a human immune system without a full body? One level would be just a container of liquid with live white and red blood cells, possibly connected to an oxygenation machine; you would insert some infected cells, then sample it or otherwise observe it periodically. If you need lung tissue or other non-blood cells for the virus to infect, then having disembodied blobs of flesh with blood vessels, being fed nutrients and oxygen, would be the next level.
Of course, if this testing infrastructure doesn't already exist, I imagine creating it would be too slow to help with this particular plague.
this is sort of how HIV production works in the lab, as it was explained to me. CD8+ cells (iirc) in solution with some other cell types/buffer medium are infected with some population of HIV particles, and the infection spreads to the other cells. this helps researchers see whether certain strains are replication-competent etc. you don't really need the red blood cells or oxygenation machine.
there's other approaches to make "organs on a chip" for drug trial screening, since lab models with only one type of cells don't capture the effects of other types, but it's really not fully baked yet.
No. The immune system is incompletely understood and staggeringly complex. It’s not a single performer or a band: it’s a symphony. You can examine individual parts to your heart’s desire, but the true nature of the immune system arises in the emergent properties of the system.
Your “first level” is something we already do with primary and immortalized cells and it can be a useful model. Your next level would be called co-culture and it also is something we already do. These can be static cultures or connected to flow systems or bioreactors or whatever. These are imperfect models, but they can help to yield useful answers for questions in the model’s scope. The closest fidelity to human immune systems would be animal models, and the closest of these would be Rhesus macaques, and indeed these are used for vaccine development.
I know you prefaced your ignorant question with "Ignorant question:", and I don't think it's wrong to ask questions of experts on HN. (That's one of the best things about this site!) However, I'm downvoting you anyway because, despite that preface, you seem to be falling into the trap of a smart geek in one field vastly (vastly!) oversimplifying the complexities of another field, and acting as if all we needed to solve this problem was for someone like yourself to come up with this fantastic idea.
No, you can't approximate a human immune system with red and white blood cells in a container of liquid. No, adding some other cells in there won't help. If that were effective, we'd be doing it already. You are either overestimating your own ingenuity or underestimating the ingenuity of tens of thousands of scientists, doctors, and engineers.
Alternatively, OP could be answered by someone saying that this is already being done. And apparently it is in some form, according to a sibling comment of yours. Maybe that’s incorrect, but you chose the least charitable interpretation instead of “Hey, here’s an idea. Why doesn’t it work like I think it would, and does it have any uses in any form?”
The question was, "is it possible to have something resembling a human immune system without a full body?"
The answer is no, for somewhat obvious reasons. The human immune system involves many organs and tissues and cells working together in very complex ways.
And I think your charitable interpretation is quite a bit too charitable. OP did not say anything like "why doesn't it work like I think it would".
My last sentence shows that I don't think my comment is going to save us from (or even help with) this pandemic. I also chose to ask it in a thread towards the bottom where the OP is answering not-new concerns. I think you have pattern-matched me (well, you say as much) and have read some intentions into my comment.
For the record, my main intention was to get an expert to say something that would gratify my curiosity and that of other readers. I hadn't heard of it before, so I assumed it was likely impractical at the moment, but guessed that technology would eventually get there.
Also, are you an expert in this field? Your sibling comment seems to be saying "yes they are working on it, no it's not practical yet except for HIV" (I presume because HIV infects white blood cells), which is at odds with your second paragraph. (Edit: Though, to be very precise, the examples from the sibling comment are about measuring infectivity and—I guess—the impact of drugs, not immune response.) It would be ironic if a non-expert gave an ignorant dismissal of a question for being ignorant.
I understand the concept of an attenuated strain. I don't see why the deletion mutants have to be found in the wild - it's easy enough to delete or modify genes in the lab to create an attenuated strain. For example, some groups have replaced VSV's glycoprotein with the coronavirus spike protein.
And as I said, you can't know if the people who had mild infections did so because the virus was deficient or whether their immune response was good. It's not enough to have the antigen, you also need the right adjuvant to mount a response. The last thing you want is to have antibodies that recognize the virus, but do not activate the immune system.
The fact that the live attenuated approach worked with polio doesn't mean that it'll work with coronavirus, and if we're not careful we could accidentally worsen the situation.
I agree that this is worthwhile area of pursuit, but one that will take a long time to bear fruit. Maybe you think that studying the variants in the wild will allow us to skip over some animal studies with the live attenuated virus, but I doubt they can be skipped.
I have no background in this whatsoever, so feel free to ignore my comment, but my guess is that finding them in the wild along with a large-enough (and representative-enough) infected population without severe symptoms basically saves the work of trying 5k different possible variant in animals — just skip the the promising candidate directly, no?
That is right. We don’t know what mutations might make the virus attenuated (mild), but we can use what Nature has done to tell us. We also get human data on safety thrown in for free. This makes a huge difference in how quickly we can use a new strain in people even under controlled conditions.
I like the idea of pairing clinical data with virus sequence information from infected patients. That seems like medicine of the future.
However, the PCR-based diagnostic tests that are current being used rely on amplifying only a small part of the virus genome so we are actually blind to how the rest of the virus is changing in the larger population (at least in routine diagnostic tests).
You showed as greyed out, which can only mean people downvoted you which I simply cannot understand: you said valid things, which I cannot believe were downvoted. What happened?
I'm only guessing, but I don't think this is likely. To the contrary, I think you are being downvoted by people who think you aren't taking the virus seriously enough. They fear that your approach will be used by people who want open up the economy before it's safe, feel you are being presumptuous in thinking you as an individual can change the outcome of the disease, and believe the best we can do is to trust the official experts. I think it's political. I think you are essentially being hit by "friendly fire" by people who think you are aiding the enemy. But this is only a guess, assuming the downvotes correspond to the negative comments. It would be nice to know what people are actually thinking.
There are almost certainly significant "Reopen All The Things" brigades running active on social media and nuking anything that might go against their agenda. HN is no exception.
You can see this in early and Layer 1/2 posts that go negative while later and Layer 3/4 thread posts that get high amounts of positive upvotes after the initial wave has moved on.
Heavy emphasis on "candidate". How can you tell if people had a mild case because the virus had deletions or because they mounted an appropriate immune response? It's not clear that the vaccine will be protective.